WO1996023779A1 - Ether derivative - Google Patents

Abstract

A novel taxol derivative having an antitumor effect and represented by formula (I), wherein R1 represents phenyl; R2 represents alkyl, alkenyl, alkynyl, cycloalkyl or alkoxy; R3 represents hydroxy, hydrogen or halogeno; R4 represents alkyl, alkenyl or alkynyl; R5 represents hydrogen, hydroxy, halogeno or alkyl; R6 represents hydrogen, hydroxy, halogeno or alkyl; R7 represents alkyl, alkenyl, alkynyl, cycloalkyl, aryl or a heterocycle; and R8 represents alkyl, aryl or alkoxy.

Description

 明

 Ether derivatives

 TECHNICAL FIELD The present invention relates to a novel taxol derivative having an antitumor fistula action.

 Taxol is a natural product represented by the following chemical structural formula, and can be obtained in trace amounts from the roots of western yew.

Taxol is known to have antitumor activity, and its mechanism of action is based on the inhibitory effect of microtubule depolymerization on cell division. Its clinical application as a carcinoma drug is expected.

Until now, taxol was only available in trace amounts from nature. In recent years, a taxol precursor represented by the following formula, which can be obtained in relatively large amounts from yew vegetables, etc., is 10-0-0-deacetylbaccatin III.

A taxol derivative semi-synthesized by using as a raw material has begun to be reported (Japanese Unexamined Patent Publication (Kokai) No. 03-5705725). Among them, a compound having a structure represented by the following formula (Taxotere) is attracting attention as a compound having an antitumor activity equal to or higher than that of Taxol, and is currently being developed as an antitumor fistula.

However, although taxol and taxotere derivatives are promising anti-tumor pain agents, clinical trials have shown that they have low efficacy against gastrointestinal cancers, especially colorectal cancer. Is desired. Also, taxol and Taxotere derivatives are also known to have low water solubility, Disclosure of the invention

 Conventionally, as the substituent at the 10-position of the taxol derivative, an acetoxyl group, a hydroxyl group, and the hydroxyl group further substituted with an asinole group, an alkylaminocarbonyl group (EP524093), and the like have been reported. A derivative having no substituent at the 0 position [Tetrahedrone Letter, 34_, 4921 (1993)] is also known. As a result of intensive studies, the present inventors have found that a derivative having an ether type substituent introduced at the 10-position has strong antitumor activity and can improve water solubility, and thus completed the present invention.

 The present invention provides a compound represented by the general formula (I)

[Where,

R ¹ is a phenyl group

 (The phenyl group may have, as a substituent, one or more groups selected from the group consisting of a halogen atom, an alkyl group and an alkoxyl group.)

Means

R ² is an alkyl, alkenyl, alkynyl, cycloalkyl or alkoxyl group (These alkyl, alkenyl, alkynyl, cycloalkyl and alkoxyl groups include a halogen atom, a hydroxyl group, a carboxyl group, an alkoxyl group, an aryloxy group, a phenyl group, an amino group, an alkylamino group, an alkoxycarbonyl group, The substituent may have one or more groups selected from the group consisting of an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group. , Alkenyl, alkynyl, cycloalkyl and alkoxyl groups.)

Means

R ³ represents a hydroxyl group, a hydrogen atom or a halogen atom. R ³ may form the following partial structure together with the methyl group bonded to the 8-position.

R is an alkyl, alkenyl, or alkynyl group

(These alkyl groups, alkenyl groups and alkynyl groups include carboxyl groups, alkoxyl groups, aryloxy groups, alkoxycarbonyl groups, aryloxy groups, cyano groups, hydroxyl groups, amino groups, alkylamino groups, acyl groups, and acyl groups. It may have, as a substituent, one or more groups selected from the group consisting of a lumino group, an acyloxy group, an alkoxycarbonylamino group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, an aryl group and a heterocyclic group. The substituent may be substituted at any position of the alkyl group, alkenyl group and alkynyl group, and the aryl group and the double-ring group are further substituted with a carboxyl group, an alkyl group, an alkoxyl group, an aryloxy group, or an alkoxy group. Carbonyl group, Consists of a phenyloxycarbonyl group, a cyano group, a hydroxyl group, an amino group, an alkylamino group, an aminoalkyl group, an acyl group, an acylamino group, an acyloxy group, an alkoxycarbonylamino group, an alkylthio group, an alkylsulfinyl group, and an alkylsulfonyl group May have one or more substituents selected from the group No. The substituent may be substituted at any position of the aryl group and the complex group. )

Means

R ⁵ represents a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group.

R ⁶ represents a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group.

R ⁷ is an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclic group

 (These alkyl groups, alkenyl groups, alkynyl groups, cycloalkyl groups, aryl groups, and heterocyclic groups include halogen atoms, hydroxyl groups, carboxyl groups, alkyl groups, alkoxyl groups, aryloxy groups, phenyl groups, amino groups, and alkylamino groups. Group may have, as a substituent, one or more groups selected from the group consisting of aminoalkyl, alkylaminoalkyl, alkoxycarbonyl, aryloxycarbonyl, acyl, acylamino and acyloxy. The substitution position of the substituent may be any of the alkyl group, alkenyl group, alkynyl group, cycloalkyl group, aryl group and heterocyclic group.

Means

R ^B is an alkyl group, aryl group or alkoxyl group

 (These alkyl groups, aryl groups or alkoxyl groups include a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxyl group, an aryloxy group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, and an alkylaminoalkyl group. And may have one or more groups selected from the group consisting of an alkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group as a substituent. May be the position of L of the alkyl group, aryl group and alkoxyl group, or a shift position.)

Means ]

And a salt thereof.

 Next, terms used in the present specification will be explained.

As used herein, in the sense of "d ~ C s" as from 1 to 6 carbon atoms, for example, "C ₂ -C ₆ alkenyl group" means an alkenyl group having 2 to 6 carbon atoms I do.

 The “alkyl group”, “alkenyl group” and “alkynyl group” may be linear or branched, and preferably have 1 to 6 carbon atoms (in the case of alkenyl and alkynyl groups) from 6 carbon atoms.

 The “alkoxyl group” means a group in which an alkyl group is bonded to the group —0—, and may be a group in which the alkyl group is substituted by a phenyl group (which may have a substituent). Specific examples include benzyloxy, phenethyloxy, p-methoxybenzyloxy and the like. The alkyl moiety preferably has 1 to 6 carbon atoms.

 The “alkoxycarbonyl group” means a group in which an alkyl group is bonded to an oxygen atom of the group CO 0—, which is substituted by a phenyl group (which may have a substituent). Such examples include benzyloxycarbonyl, phenethyloxycarbonyl, p-methoxybenzyloxycarbonyl and the like. The alkyl moiety preferably has 1 to 6 carbon atoms.

 The “aryl group” means a monovalent group obtained by removing one hydrogen atom from the nucleus of an aromatic hydrocarbon, and includes, for example, phenyl, tolyl, bifXnilyl, naphthyl and the like.

 The bonding position of the amino group in the “aminoalkyl group” may be any position of the alkyl group. The alkyl group preferably has 1 to 6 carbon atoms.

 "Alkylamino group" refers to an amino group substituted with one alkyl group or an amino group substituted with two alkyl groups (the two alkyl groups may be the same or different). Means Further, the alkyl group preferably has 1 to 6 carbon atoms. C The “acyl group” means a carbonyl group (—CO—) to which a hydrogen atom, an alkyl group or an aryl group is bonded, for example, formyl, acetyl , Propanol, benzoyl and the like. The alkyl group to be bonded is preferably one having 1 to 6 carbon atoms, and the aryl group to be bonded is preferably a phenyl group.

"Heterocyclic group" refers to a monocyclic or bicyclic ring containing one or more atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom as constituent atoms of a ring structure. Means a substituent derived from a saturated or unsaturated heterocyclic compound, These heterocyclic groups may be bonded at any position. Monocyclic compound groups include, for example, pyrrole, furan, thiophene, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, imidazole, pyrazole, imidazolidine, virazolidine, oxazole, thiazole, oxazine diazole, thiadiazole, Substituents derived from monocyclic compounds such as pyridin, dihydropyridine, tetrahydropyran, piperidine, pyridazine, pyrimidine, virazine, piperazine, dioxane, pyran, and morpholine. Examples of the bicyclic heterocyclic group include substituents derived from a bicyclic heterocyclic compound such as benzofuran, indolizine, benzothiophene, indole, naphthyridine, quinoxaline, quinazoline, and chroman.

 "Expression

(X means oxygen atom, sulfur atom, S = 0, CH ₂ CH——, ΝΗ or Ν—Υ, and Y means an alkyl group.)

A 5- to 6-membered saturated heterocyclic group containing a nitrogen atom represented by the formula (The heterocyclic group has one or more alkyl groups on carbon atoms constituting the ring. ")" Means a substituent derived from a saturated heterocyclic compound having a size of 5 to 6 members containing at least one nitrogen atom as a constituent atom of the heterocyclic group. Examples thereof include pyrrolidine, imidazolidine, villazolidine, oxazolidine, thiazolidine, isoxoxazolidine, isothiazolidine, piperidine, piperazine, morpholine, thiomorpholine, and thiomorpholine-1-oxide. Preferred examples of each substituent in the formula (I) are listed below.

The “alkyl group” and the “alkoxyl group” as substituents of the phenyl group of R ¹ preferably have 1 to 3 carbon atoms.

The number of substituents of the phenyl group of R ¹ is preferably 1 or 2, and The substitution position is preferably a meta position.

 R ′ is preferably a fluorine group, a chlorine atom, a phenyl group in which one or two methyl groups or methoxy groups have been substituted at the meta position, or an unsubstituted phenyl group.

R ² is preferably an alkyl group, an alkoxyl group or a cycloalkyl group

As the “alkyl group” for R ² , a C, to C ₆ alkyl group is preferable, and a methyl group and an ethyl group are particularly preferable. A propyl group is preferred.

The “alkoxyl group” for R ² is preferably a C 1, to C ₆ alkoxyl group, and particularly preferably a methoxy group or an ethoxy group.

As the “cycloalkyl group” for R ² , a C ₃ -C ₆ cycloalkyl group is preferred, and a cyclopropyl group is particularly preferred.

R ² is particularly preferably a methyl group, an ethyl group, a propyl group, a methoxy group, an ethoxyquin group or a cyclopropyl group.

As the “halogen atom” for R ³ , a fluorine atom is preferable.

R ³ is preferably a hydrogen atom or a hydroxyl group.

R ⁴ is preferably an alkenyl group or an alkyl group. (The alkyl group is a carboxyl group, an alkoxyl group, an aryloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, a cyano group, a hydroxyl group, an amino group, an alkylamino group, an acyl group, an acylamino group, an acyloxy group, an alkoxycarbonyl group. The aryl group and the heterocyclic group may have one or more substituents selected from the group consisting of an amino group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, an aryl group and a heterocyclic group. The group further includes a carboxyl group, an alkyl group, an alkoxyl group, an aryloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, a cyano group, a hydroxyl group, an amino group, an alkylamino group, an acyl group, an unamino group, an alkoxy group, and an alkoxy group. Aryloxycarbonyl § amino group, alkyl thio group, an alkylsulfinyl group selected from the group consisting of Le group and an alkylsulfonyl group which may have one or more as a substituent.)

As "alkyl group" for R, C, -C ₆ alkyl group is preferable, especially methylcarbamoyl group, Echiru group, a propyl group. As the “alkenyl group” for R ⁴ , a C ₃ -C ₆ alkenyl group is preferred. An aryl group is particularly preferred.

As the substituent of the alkyl group for R ⁴ , an alkylamino group or a heterocyclic group is preferable.

 In heterocyclic groups the formula

(X means oxygen atom, sulfur atom, S = 0, CH ₂ , CH—Y, ΝΗ or Ν—Υ, and Υ means an alkyl group.)

A 5-membered ring or a 6-membered saturated heterocyclic group containing a nitrogen atom represented by the formula (The double-stranded ring group has one or more alkyl groups on carbon atoms constituting the ring. It may have a plurality.

Alkyl moiety of the alkylamino group is preferably -C ₃ Arukinore group or a dialkyl kill substituted. (In the case of dialkyl substitution, the two alkyl groups may be the same or different.)

 Expression

(X means oxygen atom, sulfur atom, S = 0, CH ₂ , CH—Y, ΝΗ or Ν—Υ, and Υ means an alkyl group.)

A 5- or 6-membered saturated heterocyclic group containing a nitrogen atom represented by the formula (wherein the heterocyclic group has one or more alkyl groups on a carbon atom constituting the ring) Among them, a group derived from pyrrolidine, piperidine, piperazine, morpholine, and thiomorpholine is particularly preferable. Υ is C, ~ C ₃ al Kill groups are preferred.

The alkyl group substituted on carbon atoms which is a component of a ring of the heterocyclic group, c, to c ₃ alkyl group is preferred, a methyl group is particularly preferable.

R ⁴ is most preferably an aryl group, a morpholinoethyl group, or a thiomorpholinoethyl group.

As the “halogen atom” for R ⁵ and R ⁶ , a fluorine atom, a chlorine atom and a bromine atom are preferable.

As the “alkyl group” for R ⁵ and R ⁶ , a methyl group, an ethyl group, and a propyl group are preferable.

R ⁵ is preferably a halogen atom or a hydroxyl group, and among the halogen atoms, a fluorine atom is particularly preferred.

R ⁶ is preferably a halogen atom, a hydrogen atom or an alkyl group. Among the halogen atoms, a fluorine atom is particularly preferred. Among the alkyl groups, a methyl group is particularly preferred.

Most preferred as R ⁵ and R ^6, R ⁵ is a fluorine atom and R ⁶ is a combination of fluorine atom, R ⁵ is a hydroxyl group, those R ^e is a combination of hydrogen atoms, Oh Rui R ⁵ is a hydroxyl group , R ⁶ force A combination of butyl groups is exemplified.

R ⁷ is preferably an aryl group, a heterocyclic group, or an alkenyl group.

As the “aryl group” for R ⁷ , a phenyl group is preferable.

As the “alkenyl group” for R ⁷ , 2-methyl-1-propenyl is preferable.

The heterocyclic group represented by R ⁷ is preferably a monocyclic heterocyclic group, and more preferably a monocyclic 5- or 6-membered heterocyclic group. Examples thereof include pyrrole, furan, and thiophene. , Pyrrolidine, tetrahydrofuran, tetrahydrothiophene, imidazonore, pyrazole, imidazolidin, virazolidine, oxazole, thiazole, oxaziazole, thiaziazol, pyridine, dihydropyridine, tetrahydridopyran, pyridine, pyridazine, pyridazine, pyridazine , Piperazine, dioxane, pyran, morpholine and the like.

Among the heterocyclic groups represented by R ⁷ , a monocyclic 5- or 6-membered heterocyclic group having a single oxygen atom, nitrogen atom or sulfur atom as a constituent atom of the ring structure is particularly preferred. Preferable examples include groups derived from pyrrole, furan, thiophene, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, pyridine, dihydropyridine, tetrahydropyran, piperidine, pyran and the like.

Among the heterocyclic groups represented by R ^7, a monocyclic 5- or 6-membered heterocyclic group, which is an unsaturated heterocyclic group containing one oxygen atom, nitrogen atom or sulfur atom as a constituent atom of the ring structure Is the most preferable, and specifically, a group derived from furan, pyridine, or pyrrole is most preferable.

As R ⁷ , a 2-methyl-11-propenyl group, a phenyl group, a furyl group, a pyridyl group and a pyrrolyl group are particularly preferred.

R ⁸ is preferably an aryl group or an alkoxyl group.

As the “aryl group” for R ⁸ , a phenyl group is preferable.

As the “alkoxyl group” for R ^8, a tertiary butoxy group is preferable.

R ⁸ is particularly preferably a phenyl group or a tertiary butoxy group.

R 'is Fuweniru group, R ² is a methyl group, Echiru group, a propyl group, main butoxy group, Etokin group or a cyclopropyl group, R ³ force,' as compounds included in the present application a hydrogen atom or a hydroxyl group, IT is Ariru group , morpholinoethyl group or thiomorpholino ethyl Le group, R ⁵ is hydroxyl, R ⁶ force, 'hydrogen atom, R ⁷ is Fuweniru group, a furyl group or a 2-methyl-1 one propenyl group, R ⁸ is a tertiary butoxy The compound that is the group is most preferred.

 In the present invention, the following configuration is preferable.

Further, the configuration at the 3′-position to which the substituent R ⁷ is bonded is preferably a configuration having the same configuration as that of natural taxol, which includes both configurations.

 Among the compounds of the present invention, those having the following structures can also be mentioned as preferred examples.

and

The taxonole derivative of the present invention may be in a free form, but may be in the form of an acid addition salt. Examples of the acid addition salt include hydrochloride, sulfate, nitrate, hydrobromide, and hydrochloride. Inorganic acid salts such as hydroperoxide and phosphate, or acetate, methanesulfonate, benzenesulfonate, toluenesulfonate, citrate, maleate, fumarate, lactate, etc. Organic acid salts.

 The production method of the compound of the present invention will be described.

(In the above reaction formula, R ^{2 1} denotes a R ² that is protected by R ² and a protecting group (when R ² is substituted with a hydroxyl group Ya Amino group).

R ³¹ represents a hydrogen atom, a halogen atom or a protected hydroxyl group.

 Represents a hydrogen atom, an alkyl group, an alkenyl group, an aryl group, an alkoxycarbonyl group or the like, and is preferably a vinyl group, a fuunyl group or the like.

 X means a group which acts as a halogen atom such as iodine or bromine or a leaving group such as a methanesulfonyloxy group ゃ p-toluenesulfonyloxy group.

R ⁵¹ represents a hydrogen atom, a protected hydroxyl group, a halogen atom or an alkyl group. R ⁶¹ represents a hydrogen atom, a protected hydroxyl group, a halogen atom or an alkyl group o

R ⁷¹ means R ⁷ that is protected by R ⁷ and the protecting group (if R ⁷ is substituted with a hydroxyl group Ya Amino group).

R ⁸¹ means R ⁸ that is protected by R ⁸ and protecting group (if R ⁸ is substituted with a hydroxyl group Ya Amino group).

R ⁹ and R ¹¹¹ each independently represent a hydrogen atom, an alkyl group, an aryl group, or the like, and it is preferable that both are a methyl group or that one is a p-methoxyphenyl group and the other is a hydrogen atom .

 Examples of the hydroxyl- or amino-protecting group include silyl-based protecting groups such as triethylsilyl group and tert-butyldimethylsilyl group, 1-ethoxyshethyl group, 2,2,2-trichloromouth ethoxycarbonyl group, and benzyl group. )

 First, a compound represented by the formula (1) (hereinafter, referred to as compound (1), and compounds represented by other numbers as well) and a compound (2) are treated in a solvent in the presence of a base. The compound (3) is obtained by selectively etherifying the hydroxyl group at the 10-position.

 The solvent is preferably inert to the reaction, and examples thereof include tetrahydrofuran, N, N-dimethylformamide, and dimethylsulfoxide.

 Examples of the base include normal butyl lithium and sodium hydride. Next, the compound (3) is condensed with the compound (4), the compound (5) or the compound (6) by various methods known in the art, and if necessary, further subjected to a conversion reaction to thereby give the compound. (7) can be obtained.

The condensation reaction using the compound (4) or (5) involves the activity of a carboxylic acid such as di (2-pyridyl) dicarbonate dicyclohexylcarposimid in the presence of a base catalyst such as 4-dimethylaminopyridine. There is a method using an agent. When compound (4) is used, R ⁵ ′ and R ⁶ ′ are a combination of a hydrogen atom and a hydroxyl group.

As a condensation reaction using the compound (6), there is a method using a base such as sodium hexamethylzine razide. Finally, if necessary, the R "of compound (7) is converted by a general organic chemical conversion reaction (before compound (3) is condensed with compound (4), compound (5) or compound (6). Alternatively, R ⁴ ′ of compound (3) may be converted.), And the desired product can be obtained by removing various protecting groups.

To obtain the target compound in which R ³ is a hydrogen atom, for example, after obtaining a compound (3) in which R ³¹ is a protected hydroxyl group, the protecting group is removed, and R ³ ′ is converted to a hydroxyl group. The hydroxyl group is removed by a method known in the literature (for example, Journal of Organic Chemistry U. Org. Chem.), 58, 5028 (1993)), and a compound in which R ³ is a hydrogen atom ( After 3) is obtained, a condensation reaction with the compound (4), (5) or (6), conversion of the 10-position, if necessary, and deprotection may be carried out in the same manner as described above. There is also a method of first synthesizing a compound (1) in which R ³¹ is a hydrogen atom, converting the compound into a compound (3), performing a condensation reaction, and converting the 10-position to obtain a target product.

In order to obtain a target compound in which R ³ is a halogen atom, for example, a compound in which R ³ is a fluorine atom, after obtaining a compound (3) in which R ³¹ is a protected hydroxyl group, the protecting group is removed, R ³ 'is converted to a hydroxyl group. After that, the compound (3) in which R ³ is a fluorine atom is obtained by treating with tetrahydrofuran, methylene chloride, ethyl ether, toluene, 1,1 dimethyloxetane or the like or a mixed solvent thereof with getylaminosulfur trifluoride. The condensation reaction with the compound (4), (5) or (6), the conversion of the 10-position, if necessary, and the deprotection reaction may be carried out in the same manner as described above. In addition, there is a method in which a compound (1) in which R ³¹ is a fluorine atom is first synthesized, then converted to a compound (3), and a condensation reaction and conversion of the 10-position are performed to obtain an intended product.

Further, a compound having a R ′ force << substituted phenyl group can be obtained, for example, by subjecting the 2-position ester of the obtained compound (7) to a method described in the literature (Tetrahedron Letter,, 8931 (1994)). Is selectively hydrolyzed and then acylated. The compound (1), which is a production raw material, can be synthesized from 10-0-deacetylbaccatin III, wherein R ¹ is a fuundyl group, R Compounds in which the ² ′ is a methyl group are known in the literature (eg, Journal of American Chemical Society (J.A. m. Chem. Soc.), 110, 5917 (1988))

The compound (1) in which R ² is an alkyl group other than a methyl group can be produced as follows.

(In the formula, R "represents a hydroxyl-protecting group, and is preferably a triethylsilyl group, a 2,2,2-trichloroethoxycarbonyl group, or a benzyl group.

R ¹ and R ³¹ are the same as above. )

0 First, compound (8) is oxidized (eg, treated with manganese dioxide in an inert solvent (eg, dioxane) at room temperature or under heating) to obtain compound (9).

Next, the compound (9) is reacted with a base in a solvent inert to the reaction (such as tetrahydrofuran) at a reaction temperature of 100 ° C to 0 ° C, and then R ²² — Z (R ²² is an alkyl group And Z represents a halogen atom such as an iodine atom or a bromine atom, or a leaving group such as a methanesulfonyl group or a balatoluenesulfonyl group.) By reacting from C at room temperature, compound (10) is obtained. Examples of the base used include lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, lithium diisopropylamide, tert-butoxypotassium, and sodium hydride. The amount may be 1 to 10 equivalents based on compound (9).

 The compound (11) can be obtained by subjecting the obtained compound (10) to {reaction with a reducing agent (such as sodium borohydride) in a solvent (such as methanol-tetrahydrofuran)}.

By removing the protecting group at position 10 of compound (11), compound (1) in which R ² is an alkyl group other than a methyl group can be obtained.

 Compound (4), compound (5) and compound (6), which are raw materials for production, are prepared according to the method described in (4). Compound (5) was prepared according to the method described in Journal of American Chemical Society, 110, 519 17 (1998), and compound (6) was prepared as a tetrahedron letter, 34, According to the method described in 414 (1993), each can be synthesized.

 The compound of the present invention can be used for the treatment of various cancers such as, for example, lung cancer, gastrointestinal cancer, ovarian cancer, uterine cancer, breast cancer, liver cancer, head and neck cancer, blood cancer, kidney cancer, Kogan tumor. The compound of the present invention can be administered as various injections such as intravenous injection, intramuscular injection and subcutaneous injection, or by various methods such as oral administration and transdermal administration. Among these administration methods, intravenous administration by an aqueous preparation and oral administration are preferred. Aqueous preparations can be prepared by forming acid addition products with pharmacologically acceptable acids or by preparing alkali metal salts such as sodium. In the case of oral administration, it may be in a free form or in a salt form.

 As for the preparation method of the preparation, an appropriate preparation is selected according to the administration method, and the preparation can be prepared by various commonly used preparation methods. Among the dosage forms of the antitumor agent of the present invention, examples of oral preparations include tablets, powders, granules, capsules, solutions, syrups, elixirs, oily or aqueous suspensions, and the like. In the case of injections, stabilizers, preservatives, solubilizing agents, etc. can be used in the preparation. A solution that may contain these adjuvants may be stored in a container, and then freeze-dried or the like to form a solid preparation for use at the time of use.

Liquid preparations include solutions, suspensions, emulsions, and the like.When preparing these preparations, suspending agents, emulsifiers, and the like can also be used as additives. The compound of the present invention can be used for the treatment of cancer in mammals, especially in humans. When administered to humans, it is preferably administered once a day and repeated at appropriate intervals.

The dose is preferably in the range of about 0.5 mg to 50 mg, preferably about 1 mg to 2 Omg, per lm ² of the body surface area.

 Next, an example will be described in detail. In the examples, the following abbreviations are used.

 TES triethylsilyl group

B z benzyl group

B 0 c t e r t-butoxycarbonyl group

Ph phenyl group

 T r 0 c 2,2,2-Trichloro mouth ethoxyquin carbonyl group

TBS t er t-butyldimethylsilyl group

T f trifluoromethanesulfonyl group

 TI PS triisopropyl silinole group

MP P—Methoxy phenyl group

Ts p -Toluenesnolephonyl group

DS dimethylsilyl group

BEST MODE FOR CARRYING OUT THE INVENTION

 Example 1

Step 1: 10—0—aryl-10-deacetyl-7—0—triethylsilyl paccatin I I I

 200 mg of 10-deacetyl-7-0-triethylsilylpaccatin II was dissolved in 2 ml of dry tetrahydrofuran and cooled to -78 ° C. Thereto, n-butyllithium (1.67 M n-hexane solution, 0.277 ml) was added dropwise, and the mixture was stirred for 15 minutes. Then, 0.041 ml of allyl iodide was added to 0.5 ml of dimethyl sulfoxide. Drop the dissolved solution,

The mixture was stirred at 0 ^e C for 3 hours. A saturated aqueous solution of ammonium chloride was added to the reaction solution, extracted with ethyl acetate, washed with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-layer chromatography (developing solvent; chloroform: methanol = 40: l (v / v)) to give 156 mg of the title compound as white crystals.

Touch point: 205-209

'Η-Oki (CDCh / TMS) 5 (ppm):

 0.50-0.64 (m, 6H), 0.95 (t, 9H, J = 7H2), 1.06 (s, 3H), 1.20 (s, 3H),

1.67 (s, 3H), 1.85-1.92 (m, 1H), 2.08 (s, 3H), 2.26-2.29 (m, 2H), 2.28 (s, 3H), 2.46-2.53 (m, 1H), 3.88 (d, 1H, J = 7H2), 4.01-4.10 (m, 2H),

 4.15 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.43 (dd, 1H, J = 7Hz, 10Hz),

 4.87-4.90 (m, 1H), 4.96 (d, 1H, J = 8Hz), 5.03 (s, 1H), 5.20 (d, 1H, J = 10Hz),

5.32 (dd, 1H, J = l.5Hz, 10Hz), 5.61 (d, 1H, J = 7Hz), 5.95-6.04 (m, 1H),

 7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz)

IR (KBr): 3488, 3080, 2956, 2884, 2744, 1724, 1652, 1604, 1586 cm " ¹ MS-FAB: 699 (MH ⁺ )

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3-phenyl-2- (triethylsilyloxy) propionyl] -10-0-aryl-10-decetyl- 7-0 — Triethylsilyl paccatin III

 Dissolve 100 m of the compound obtained in the above step 1 and 108 mg of (3R, 4S) -1-tert-butoxycarbonyl-4-phenyl-3- (triethylsilyloxy) azetidin-2-one in 2 ml of dried tetrahydrofuran. Then -40. Cooled to C. Then, lithium bis (trimethylsilyl) amide (1M tetrahydrofuran solution, 0.572 ml) was added dropwise, and the mixture was stirred for 15 minutes. A saturated aqueous solution of ammonium chloride was added, extracted with ethyl acetate, washed with saturated saline, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel thin eye chromatography (developing solvent: ethyl acetate: hexane = 1: 4 (v / v)) to give 126 mg of the title compound as a colorless amorphous Obtained as a porous solid.

Ή-NMR (CDCU / TMS) δ (ppm):

 0.31-0.52 (m, 6H), 0.54-0.62 (m, 6H), 0.79 (t, 9H, J = 7Hz),

 0.96 (t, 9H, J = 7Hz), 1.24 (s, 6H), 1.32 (s, 9H), 1.69 (s, 3H), L 90 (s, 3H),

2.15-2. 22 (m, 1H), 2.34-2.41 (m, 1H), 2.45-2. 54 (m, 1H), 2.53 (s, 3H),

 3.85 (d, 1H, J = 7Hz), 4.00-4.13 (m, 2H), 4.19 (d, 1H, J = 8Hz),

 4.31 (d, lH, J = 8Hz), 4.41 (dd, 1H, J = 7Hz, 10Hz), 4.56 (s, 1H),

 4.95 (d, 1H, J = 8Hz), 4.98 (s, 1H), 5.20 (d, 1H, J = 12Hz), 5.29 (br.1H),

 5.32 (dd, lH, J = 1.5Hz, 12Hz), 5.47 (br, 1H), 5.68 (d, lH, J = 7Hz),

 5.94-6. 02 (m, 1H), 6.31 (t, 1H, J = 8Hz), 7.27-7.31 (m, 3H),

7.37 (t, 2H, J = 8Hz), 7.48 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz)

Step 3: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3--3-phenylpropionyl] -10-0-aryl-10-deacetylbacca Tin III 45.5 mg of the compound obtained in Step 2 above was dissolved in 2 ml of acetonitrile and -10. Cooled to C. Next, 0.035 ml of 12N hydrochloric acid aqueous solution was added dropwise, and the mixture was stirred for 1 hour. An aqueous saturated sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate, washed with saturated saline, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: methanol = 20: 1 (v / v)) to give 23.5 mg of the title compound as a white solid. Obtained as a solid.

Melting point: 156-160 ° C

_{Ή-NR (CDC1 3 / TMS} ) «5 (ppm):

 1.22 (s, 6H), 1.35 (s, 9H), 1.69 (s, 3H), 1.80-1.82 (m, 1H), 1.83 (s, 3H),

2.28 (m, 2H), 2.36 (s, 3H), 2.53- 2.61 (m, 1H), 3.39 (br, 1H),

 3.86 (d, 1H, J = 7Hz), 4.05 (dd, 1H, J = 6Hz, 13Hz), 4.16-4.20 (m, 3H),

 4.30 (d, 1H, J = 8Hz), 4.62 (s, lH), 4.94 (d, 1H, J = 8Hz), 5.04 (s, 1H).

 5.22 (dd, 1H, J = 1.5Hz, 10Hz), 5.26 (br, 1H), 5.32 (dd, 1H, J = 1.5Hz, 17.5Hz),

5.40 (brd, 1H, J = 10Hz), 5.68 (d, 1H, J = 7Hz), 5.89-5.99 (m, 1H),

 6.22 (t, 1H, J = 8Hz), 7.30-7.42 (m, 5H), 7.9 (t, 2H, J = 8Hz),

 7.61 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz)

IR (Br): 3464, 3076, 2984, 2944, 2904, 1720, 1604, 1586 cm— ¹

MS-FAB: 849 (MH ⁺ )

Example 2

Step 1: 13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -3-fuunyl-2- (triethylsilyloxy) propionyl] -10-deacetyl-10-O-formylmethy Le-7—0—Triethylsilyl paccatin III

 126 mg of the compound obtained in Step 2 of Example 1 and 41.0 mg of N-methylmorpholine-N-oxide were added to a mixed solvent of 10 ml of acetone and 3 ml of water, and 0.6 mg of osmium tetroxide was added thereto at room temperature. Stirred for hours. After adding sodium sulfite and stirring for 15 minutes, further adding anhydrous sodium sulfate and stirring for 30 minutes, the insoluble matter was removed by filtration. The solvent was distilled off under reduced pressure, and the resulting residue was dissolved in methanol (4 ml). Under ice cooling, a solution of sodium metaperiodate (50.0 mg) in water (1 ml) was added dropwise and the mixture was stirred for 30 minutes. A saturated aqueous solution of ammonium chloride was added, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel thin-layer chromatography (developing solvent; chloroform: methanol = 40: Kv / v) to give 98.5 mg of the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) δ (ppm):

 0.31-0.48 (m, 6H), 0.54-0.61 (m, 6H), 0.79 (t, 9H, J = 7Hz),

0.96 (t, 9H, J = 7Hz), 1.25 (s, 3H), L26 (s, 3H), 1.31 (s, 9H), 1.70 (s, 3H), 1.91 (s, 3H), 2.15-2.22 ( m, 1H), 2.34-2.40 (m, 1H), 2.45-2.53 (m, 1H), 2.53 (s, 3H), 3.48 (s, 1H), 3.81 (d, 1H, J = 7Hz), 4.18 (s, 1H),

 4.19 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz), 4.44 (dd, 1H, J = 7Hz, 10Hz),

 4.56 (s, lH), 4.95 (d, 1H, J = 8Hz), 5.12 (s, 1H), 5.30 (br, 1H), 5.47 (br, 1H), 5.68 (d, 1H, J = 7Hz), 6.31 (t, 1H, J = 8Hz), 7.29-7.39 (m, 3H),

 7.37 (t, 2H, J = 8Hz), 7.48 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz),

 8.12 (d, 2H, J = 8 Hz), 9.85 (s, 1H)

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3-phenyl-2- (triethylsilyloxy) propionyl] -10-deacetyl-10-O- (2-morpholinoethyl) -7-0—triethylsilylpaccatin III

 98.5 mg of the compound obtained in the above step 1, 0.080 ml of morpholine and 0.052 ml of acetic acid were dissolved in 8 ml of ethanol, and 57.0 mg of sodium cyanoborohydride was added, followed by stirring at room temperature for 1 hour. The mixture was diluted with black hole form, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the obtained residue was purified by silica gel thin-eye chromatography (developing solvent; black form: methanol = 40: 1 (v / v)), and 91.6 mg of the title compound was colorless. As an amorphous solid.

 Ή-NMR (CDC / TMS) δ (ppm):

 0.31-0.49 (n 6H), 0.52-0.64 (m, 6H), 0.79 (t, 9H, J = 7Hz),

 0.95 (t, 9H, J = 7Hz), 1.21 (s, 3H), 1.22 (s, 3H), 1.32 (s, 9H), 1.68 (s, 3H), 1.91 (s, 3H), 1.88-1.94 ( 1H), 2.15-2.22 (m, 1H), 2.34-2.40 (m.1H),

 2.44- 2.50 (m, 1H), 2.53 (s, 3H), 2.56-2.59 (m, 4H), 2.68 (t, 2H, J = 6Hz),

 3.62 (t, 2H, J = 6Hz), 3.73 (t, 4H, J = 5Hz), 3.84 (d, 1H, J = 7Hz),

 4.18 (d, 1H, J = 8Hz), 4.31 (d, lH, J = 8Hz), 4.41 (dd, 1H, J = 7Hz, lOHz),

 4.56 (s, 1H), 4.94 (s, 1H), 4.95 (d, 1H, J = 8Hz), 5.30 (br, 1H), 5.48 (br, 1H), 5.67 (d, 1H, J = 7Hz), 6.30 (t, 1H, J = 8Hz), 7.28-7.32 (m, 3H),

 7.37 (t, 2H, J = 8Hz), 7.48 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz),

 8.12 (d, 2H, J = 8Hz)

Step 3: 13—0 _ [(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-hydroxypropionyl] -10-deacetyl-10-O- (2-morpholinoethyl ) Power force III 91.6 mg of the compound obtained in the above step 2 was dissolved in 4 ml of acetonitrile, 0.20 ml of pyridine and 0.60 ml of a 48% aqueous hydrogen fluoride solution were added under ice cooling, and the mixture was reacted at 0 for 2 hours and at room temperature overnight. The reaction solution was ice-cooled and made weakly alkaline with a saturated aqueous solution of sodium bicarbonate. The mixture was extracted three times with ethyl acetate, washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel thin-layer chromatography (eluent: developing solvent; chloroform: methanol = 10: 1 (v / v)) to give 52.1 mg of the title compound as a white solid.

Melting point: 143-147. C

 Ή-NMR (CDC / TMS) δ (ppm):

 1.19 (s, 3H), 1.20 (s, 3H), 1.34 (s, 9H), 1.67 (s, 3H), 1.78-1.85 (m, 1H),

1.88 (s, 3H), 2.27 (m, 2H), 2.36 (s, 3H), 2.51-2.68 (m, 7H),

 3.63-3.80 (m, 6H), 3.84 (d, 1H, J = 7Hz), 4.12 (d, 1H, J = 8Hz),

 4.22 (dd, 1H, J = 7Hz, 10Hz), 4.29 (d, 1H, J = 8Hz), 4.62 (s, 1H),

 4.94 (d, 1H, J = 8Hz), 5.09 (s, 1H), 5.27 (brd, 1H, J = 10Hz), 5.44 (br, 1H),

 5.66 (d, 1H, J = 7Hz), 6.21 (t, 1H, J = 8Hz), 7.29-7.42 (m, 5H),

 7.49 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz)

IR (KBr): 3456, 3068, 2976, 2940, 1986, 1722, 1606, 1586 cm— ¹

MS-FAB: 921 (MH ⁺ )

Example 3

Step 1: 4,10-dideacetyl-4-0-propionyl-10-0- (2,2,2-trichloroethoxycarbonyl-7-7-0-triethylsilylpaccatin Π 1

2. 00 4,10-Dideacetyl-4-1-0-propionyl-13-deoxy-13-oxo-7-10-Triethylsilylpaccatin III is dissolved in pyridine (40 ml), and the mixture is cooled under ice-cooling. A solution obtained by dissolving 1.03 ml of 2-trichloroethyl in 4 ml of dichloromethane was added dropwise and stirred for 30 minutes. The reaction solution was poured into ice water and extracted with ethyl acetate. After washing with cold 0.5N aqueous hydrochloric acid, water, saturated aqueous sodium bicarbonate, and saturated saline in this order, and drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 60 ml of tetrahydrofuran, and under ice cooling, 282 m of sodium tetrahydroborate was added. After 5 minutes, 3 ml of methanol was added and the mixture was stirred for 2.5 hours. The reaction solution was diluted with chloroform, washed with a saturated aqueous solution of ammonium chloride, and dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure After that, the residue was purified by silica gel chromatography (elution solvent: ethyl acetate: n-hexane = 1: 2 (v / v)) to obtain 2.05 g of the title compound as white crystals.

Melting point: 227-228 ° C

 Ή-NMR (CDCla / TMS) δ (ppm):

 0.56- 0, 62 (m, 6H), 0.93 (t, 9H, J = 8Hz), 1.07 (s, 3H), 1.21 (s, 3H),

 1.23 (t, 3H, J = 7Hz), 1.70 (s, 3H), 1.85-1.92 (m, 1H), 2.19 (s, 3H),

 2.26-2.28 (m, 2H), 2.51-2.67 (m, 3H), 3.72 (d, 1H, J = 7Hz),

 4.16 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz), 4.50 (dd, 1H, J = 7Hz, 10Hz),

 4.81 (AB type d, 2H, J = 2Hz), 4.85 (br, 1H), 4.91 (d, 1H, J = 8Hz),

 5.63 (d, 1H, J = 7Hz), 6.30 (s, lH), 7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz)

IR (KBr): 3560, 2960, 2888, 1764, 1728, 1604, 1586 cm " ¹

MS-FAB: 849 (MH ⁺ )

Step 2: 4, 10-dideacetyl-4-10-propionyl-7-0-triethylsilylbaccatin III

 500 mg of the compound obtained in the above step 1 was dissolved in a mixed solvent of 16 ml of methanol and 4 ml of acetic acid, and 1 g of active zinc powder was added. After cooling, the insolubles were removed by filtration, and the solvent was distilled off under reduced pressure. Ethyl acetate and a saturated aqueous solution of sodium bicarbonate were added to the residue, and the organic eyebrows were dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained oil was crystallized from hexane to give the title compound (370 m) as white crystals.

Melting point: 202-204. C

Ή-NMR (CDCh / TMS) δ (ppm):

 0.48-0.63 (m, 6H), 0.94 (t, 9H, J = 8Hz), 1.07 (s, 3H), 1.24 (t, 3H, J = 7Hz), 1.26 (s, 3H), 1.73 (s, 3H ), 1.86- 1.93 (m, 1H), 2.07 (s, 3H),

 2.22-2.28 (m, 2H), 2.45-2.51 (m, 1H), 2.52-2.67 (m, 2H), 3.94 (d, 1H, J = 7Hz), 4.16 (d, 1H, J = 8Hz), 4.27 (d, 1H, J = 2Hz), 4.31 (d, 1H, J = 8Hz),

 4.42 (dd, 1H, J = 7Hz, 10Hz), 4.84 (t, 1H, J = 8Hz), 4.91 (d, 1H, J = 8Hz),

5.18 (s, 3H), 5.59 (d, 1H, J = 7Hz), 7.46 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.10-8.12 (m, 2H) IR (KBr): 3476, 3072, 2960, 2888, 1986, 1728, 1712, 1604, 1586 cm "'MS-FAB: 673 (MH

Process 3: 10-0-aryl-4,10-dideacetyl-4-1-O-propionyl-7-7-triethylsilylbaccatin I I I

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 1 of Example 1 to obtain the title compound as white crystals.

Melting point: 204-207. C

 Ή-NMR (CDC / TMS) δ (ppm):

 0.50-0.65 (m, 6H), 0.95 (t, 9H, J = 7Hz), 1.06 (s, 3H), 1.20 (s, 3H),

 1.24 (t, 3H, J = 7Hz), 1.68 (s, 3H), 1.85-1.92 (m, 1H), 2.07 (s, 3H),

 2.26 (d, 2H, J = 8Hz), 2.47-2.57 (m, 1H), 2.58-2.67 (m, 2H),

 3.88 (d, 1H, J = 7Hz), 4.05-4.07 (m, 2H), 4.15 (d.1H, J = 8Hz),

 4.29 (d, 1H, J = 8Hz), 4.44 (dd, 1H, J = 7Hz, 10Hz), 4.88-4.92 (m, 2H),

 5.04 (s, 1H), 5.20 (dd, 1H, J = l.5Hz, 10Hz), 5.31 (dd, 1H, J = l.5Hz, 17Hz), 5.60 (d, 1H , J = 7Hz), 5.95-6. 04 (m, 1H), 7.46 (t, 2H, J = 8Hz),

 7.59 (t, 1H, J = 8Hz), 8.10-8.12 (m, 2H)

IR (KBr): 3496, 3080, 2956, 2884, 2744, 1724, 1650, 1604, 1586 cm—, MS-FAB: 713 (MH ⁺ )

Step 4: 10-0-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propioni -]-4,10-dideacetyl-4-1-0-propionyl-7-0-triethylsilylpaccatin Ι 化合物 50 mg of the compound obtained in step 3 above and (3R, 4S) -l-tert-butoxycarbonyl _4_ (2-Furyl) -3- (triisopropylsilyloxy) azetidin-2-one 43 rog was dissolved in 2 ml of tetrahydrofuran and cooled to -78 ° C. Then, sodium bis (trimethylsilyl) amide (1M solution in tetrahydrofuran, 0.280 ml) was added dropwise and stirred for 15 minutes. A saturated aqueous solution of ammonium chloride was added, and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin-layer chromatography (developing solvent: ethyl acetate: n-hexane = 1: 4 (v / v)) to give 67.8 mg of the title compound. As a colorless amorphous solid Was.

 Ή-NMR (CDCh / TMS) δ (ppm):

 0.52-0.62 (m, 6H), 0.94-1.01 (m, 30H), 1.21 (s, 3H), 1.24 (s, 3H),

 1.35 (s, 9H), 1.37 (t, 3H, J = 7Hz), 1.69 (s, 3H), 1.92 (s, 3H),

 1.87-1.94 (m, 1H), 2.31-2.36 (m, 2H), 2.46-2.56 (m, 1H), 2.71-2.79 (m, 2H),

3.84 (d, 1H, J = 7Hz), 4.00-4.ll (m, 2H), 4.19 (d, 1H, J = 8Hz),

 4.31 (d, 1H, J = 8Hz), 4.42 (dd, 1H, J = 7Hz, 10Hz), 4.89 (d, 1H, J = 8Hz),

 4.99 (s, 1H), 5.20 (d, 1H, J = llHz), 5.24-5.34 (m, 3H), 5.68 (d, 1H, J = 7Hz),

 5.95-6.02 (m, 1H), 6.21 (t, 1H, J = 8Hz), 6.27 (d, 1H, J = 3.5Hz),

 6.37 (dd, 1H, J = 2Hz, 3.5Hz), 7.39 (s, 1H), 7.46 (t, 2H, J = 8Hz),

 7.57 (t, 1H, J = 8Hz), 8.11 (d, 2H, J = 8H2)

Step 5: 13— 0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisobrovirsilyloxy) propionyl] -4,10— Didacetyl -10-0 —formylmethyl -4-1-O-propionyl -7—0 _triethylsilyl baccatin III

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 1 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) <5 (ppm):

 0.53-0.63 (m, 6H), 0.94-1.01 (m, 30H), 1.22 (s, 3H), 1.25 (s, 3H),

 1.34 (s, 9H), 1.36 (t, 3H, J = 7Hz), 1.69 (s, 3H), 1.92 (s, 3H),

 2.32-2.36 (m, 2H), 2.46-2.53 (m, 1H), 2.69-2.78 (m, 2H), 3.47 (s, 1H),

 3.80 (d, 1H, J = 7Hz), 4.16 (s, 1H), 4.18 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

4.43 (dd, 1H, J = 7Hz, 10Hz), 4.90 (d, 1H, J = 8Hz), 4.98 (s, lH), 5.13 (s, 1H),

5.24- 5.30 (m, 2H), 5.68 (d, 1H, J = 7Hz), 6.20 (t, 1H, J = 8Hz),

 6.27 (d, 1H, J = 3.5Hz), 6.37 (dd, 1H, J = 2Hz, 3.5Hz), 7.39 (s, 1H),

7.47 (t, 2H, J = 8Hz), 7.57 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz), 9.85 (s, 1H) Step 6: 13-0-[( 2R, 3S) -3- (terbutoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -4,10-dideacetyl-10-〇- (2- Morpholinoethyl) -4-0-propionyl -7-0-triethylsilyl puckachi N III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 2 of Example 2 to obtain the title compound as a colorless amorphous substance.

 Ή-NMR (CDC / T S) δ (ppm):

 0.50-0.65 (m, 6H), 0.993-1.01 (m, 30H), 1.19 (s, 3H), 1.21 (s, 3H),

 1.35 (s, 9H), 1.37 (t, 3H, J = 7Hz), 1.67 (s, 3H), 1.93 (s, 3H),

 2.26-2.39 (m, 2H), 2.45-2.53 (m, lH), 2.57-2.60 On, 4H), 2.64-2.69 (m, 2H),

2.71-2.81 (m, 2H), 3.62 (t, 2H, J = 6Hz), 3.73 (t, 4H, J = 5Hz),

 3.83 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

 4.41 (dd, 1H, J = 7Hz, 10Hz), 4.89 (d, 1H, J = 8Hz), 4.95 (s, 1H), 4.99 (s, 1H),

5.24-5.31 (m, 2H), 5.67 (d, 1H, J = 7Hz), 6.20 (t, 1H, J = 8Hz),

 6.27 (d, 1H, J = 3.5Hz), 6.37 (dd, 1H, J = 2Hz, 3.5Hz), 7.39 (s, 1H),

 7.48 (t, 2H, J = 8Hz), 7.57 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz)

Step 7: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3_ (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl-10-O- (2-morpholinole

) -4-0—Propionirubaccatin III

 50.6 mg of the compound obtained in the above step 6 was dissolved in 2 ml of pyridine, and 0.40 ml of hydrogen fluoride pyridine was added thereto under ice-cooling. The mixture was stirred at 0 ° C for 10 minutes and reacted at room temperature for one hour. The reaction solution was ice-cooled and made weakly alkaline with a saturated aqueous solution of sodium bicarbonate. The mixture was extracted three times with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel thin-layer chromatography (eluent: developing solvent; methanol: methanol = 10: 1 (v / v)) to obtain 27.6 mg of the title compound as a white solid.

Melting point: 139-142. C

 Ή-NMR (CDCh / TMS) δ (ppm):

 1.19 (s, 3H), 1.21 (s, 3H), 1.29 (t, 3H, J = 7 Hz), 1.34 (s, 9H), 1.67 (s, 3H), 1.78-1.85 (m, 1H), 1.93 ( s, 3H), 2.26-2.40 (m, 2H), 2.52-2.73 (m, 9H),

 3.64-3.80 (m, 6H), 3.86 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz),

 4.27 (dd, 1H, J = 7Hz, 10Hz), 4.31 (d, 1H, J = 8Hz), 4.70 (s, 1H),

4.91 (d, 1H, J = 8Hz), 5.09 (s, 1H), 5.23 (d, 1H, J = 10Hz), 5.31 (brd, 1H, J = 10Hz), 5.68 (d, 1H, J = 7Hz), 6.23 (t, 1H, J = 8Hz),

 6.34 (d, 1H, J = 3.5Hz), 6.39 (dd, 1H, J = 2Hz, 3.5Hz), 7.43 (s, 1H),

 7.48 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz)

 IR (KBr): 3464, 2980, 2944, 2356, 1972, 1722, 1604, 1496 cm— '

MS-FAB: 925 (MH ⁺ )

 Example 4

Step 1: 4-0-Butanoyl-4,10-dideacetyl -10-0- (2,2,2-trichloroethoxycarbonyl) -7-0-Triethylsilylpaccatin ΙΠ

4-0-Butanoyl-13-dexoxy-4,10-dideacetyl-13-oxo-7-0-triethylsilylpaccatin III was reacted in the same manner as in Step 1 of Example 3 to obtain the title compound as white crystals. Was. Melting point: 227-228 ° C

 Ή-NMR (CDCh / TMS) δ (pm):

 0.52-0.62 (m, 6H), 0.93 (t, 9H, J = 8Hz), 1.06 (t, 3H, J = 7Hz), 1.07 (s, 3H), 1.21 (s, 3H), 1.70 (s, 3H ), 1.78 (q, 2H, J = 7Hz), 1.85- 1.92 (m, 1H),

 2.19 (s, 3H), 2.28 (d, 2H, J = 8Hz), 2.56 (t, 2H, J = 7Hz), 2.51-2.59 (m, 1H),

3.83 (d, 1H, J = 7Hz), 4.15 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

 4.49 (dd, 1H, J = 7Hz, 10Hz), 4.81 (AB type d, 2H, J = 2Hz), 4.85 (br, lH),

 4.92 (d, 1H, J = 8Hz), 5.63 (d, 1H, J = 7Hz), 6.30 (s, 1H), 7.47 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz) , 8. ll (m, 2H)

 IR (KBr): 3560, 2960, 2888, 1764, 1728, 1604, 1586 cm— '

MS-FAB: 849 (MH +)

Step 2: 4-0—Butanoyl-4,10-dideacetyl-7-7-0—Triethylsilylpackatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 2 of Example 3 to obtain the title compound as white crystals.

Melting point: 160-163 ° C

_{Ή-NMR (CDC1 3 / TMS} ) δ (ppm):

 0.48-0.63 (m, 6H), 0.94 (t, 9H, J = 8Hz), 1.05 (t, 3H, J = 3Hz), 1.08 (s, 6H), 1.74 (s, 3H), 1.76-1.78 (m , 2H), 1.80-1.92 (m, 1H), 2.07 (s, 3H),

 2.25 (d, 2H, J = 8Hz), 2.45-2.53 (m, 1H), 2.56 (t, 2H, J = 7Hz),

 3.94 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz), 4.25 (d.1H, J = 2Hz),

 4.31 (d, 1H, J = 8Hz), 4.42 (dd, 1H, J = 7Hz, 10Hz), 4.86 (br, 1H),

 4.91 (d, 1H, J = 8 Hz), 5.17 (s, 3H), 5.59 (d, 1H, J = 7 Hz), 7.47 (t, 2H, J = 8 Hz), 7.61 (t, 1H, J = 8 Hz) , 8.11-8.14 (m, 2H)

IR (KBr): 3484, 3076, 2968, 2888, 2744, 1714, 1606, 1586 cm " ¹

MS-FAB: 687 (MH ⁺ )

Process 3: 10-O-aryl-4-0-butanoyl-4,10-dideacetyl-7-7-0-triethylsilyl paccatin III

The compound obtained in the above Step 2 was reacted in the same manner as in Step 1 of Example 1 to convert the title compound to white. Obtained as colored crystals.

Melting point: 200-204. C

 Ή-NMR (CDC / TMS) δ (ppm):

 0.50-0.65 (m, 6H), 0.96 (t, 9H, J = 7Hz), 1.05 (t, 3H, J = 7Hz), 1.06 (s, 3H), 1.20 (s, 3H), 1.67 (s, 3H ), 1.78 (q, 2H, J = 7Hz), 1.82-1.91 (m, 1H),

 2.06 (s, 3H), 2.26 (d, 2H, J = 8Hz), 2.47-2.57 (m, 1H), 2.55 (t, 2H, J = 7Hz),

3.88 (d, 1H, J = 7Hz), 4.01-4.13 (m, 2H), 4.15 (d, 1H, J = 8Hz),

 4.29 (d, 1H, J = 8Hz), 4.43 (dd, 1H, J = 7Hz, 10Hz), 4.87-4.92 (m, 2H),

 5.03 (s, lH), 5.19 (dd, 1H, J = 1.5Hz, 10Hz), 5.31 (dd, 1H, J = 1.5Hz, 17Hz), 5.60 (d, 1H, J = 7Hz), 5.95-6.04 ( m, 1H), 7.46 (t, 2H, J = 8Hz),

 7.59 (t, 1H, J = 8Hz), 8.10-8.12 (m, 2H)

IR (KBr): 3504, 3076, 2964, 2884, 2744, 1718, 1650, 1604, 1586 cm— 'MS-FAB: 727 (MH ⁺ )

Step 4: 10—O—aryl-13-0 _ [(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl]- 4_0—butanol-4,10-dideacetyl-7—0—triethylsilylpaccatin III

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 4 of Example 3 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) δ (ppm):

 0.52-0.63 (m, 6H), 0.94-1.01 (m, 30H), 1.05 (t, 3H, J = 7Hz), 1.20 (s, 3H), 1.24 (s, 3H), 1.35 (s, 9H), 1.69 (s, 3H), 1.92 (s, 3H), 1.83- 1.95 (m, 1H),

2.25-2.36 (m, 2H), 2.46-2.56 (m, 1H), 2.58-2.63 (m, 2H), 2.76-2.80 (m, 1H),

3.85 (d, 1H, J = 7Hz), 3.99-4.11 (m, 2H), 4.18 (d, 1H, J = 8Hz),

 4.29 (d, 1H, J = 8Hz), 4.41 (dd, 1H, J = 7Hz, 10Hz), 4.89 (d, 1H, J = 8Hz),

 5.00 (s, 1H), 5.18-5.34 (m, 4H), 5.67 (d, 1H, J = 7Hz), 5.94-6.02 (m, 1H),

 6.20 (t, 1H, J = 8Hz), 6.27 (d, 1H, J = 3.5Hz), 6.37 (dd, 1H, J = 2Hz, 3.5Hz),

7.37 (s, lH), 7.46 (t, 2H, J = 8 Hz), 7.57 (t, 1H, J = 8 Hz), 8. ll (d, 2H, J = 8 Hz) Step 5: 13-0-[( 2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -4-O-butanoyl-4,10-di Deacetyl-10-O-formylmethyl-7-0-triethylsilylpaccatin III The compound obtained in the above Step 4 was reacted in the same manner as in Step 1 of Example 2 to obtain the title compound as a colorless amorphous solid. .

 Ή-NMR (CDCh / TMS) δ (ppm):

 0.53-0.65 (m, 6H), 0.94-1.01 (m, 30H), 1.05 (t, 3H, J = 7Hz), 1.22 (s, 3H), 1.25 (s, 3H), 1.34 (s, 9H), 1.69 (s, 3H), 1.83-1.94 (m, 3H), 1.92 (s, 3H),

2.27-2.39 (m, 2H), 2.48-2.53 (m, 1H), 2.54-2.63 (m, 1H), 2.74-2.81 (m, 1H),

3.47 (s, 1H), 3.81 (d, 1H, J = 7Hz), 4.16 (s, 1H), 4.18 (d, 1H, J = 8Hz),

 4.30 (d, 1H, J = 8Hz), 4.44 (dd, 1H, J = 7Hz, 10Hz), 4.89 (d, 1H, J = 8Hz),

 4.99 (s, 1H), 5.14 (s, 1H), 5.25 (d, 1H, J = 10Hz), 5.31 (d, 1H, J = 10Hz),

 5.67 (d, 1H, J = 7Hz), 6.19 (t, 1H, J = 8Hz), 6.27 (d, 1H, J = 3.5Hz),

 6.36 (dd, 1H, J = 2Hz, 3.5Hz), 7.37 (s, 1H), 7.47 (t, 2H, J = 8Hz),

 7.58 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz), 9.85 (s, 1H)

Step 6: 13— 0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -4-0— Butanoyl-4,10-didecyl -10-O- (2-morpholinoethyl) -7-0—Triethylsilyl paccatin I II

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 2 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) δ (ppm):

 0.50-0.64 (m, 6H), 0.94-1.03 (m, 30H), 1.05 (t, 3H, J = 7Hz), 1.19 (s, 3H), 1.21 (s, 3H), 1.35 (s, 9H), 1.67 (s, 3H), 1.93 (s, 3H), 1.83-1.93 (m, 3H),

2.25-2.39 (m, 2H), 2.45-2.53 (m, 1H), 2.57-2.81 (m, 8H), 3.62 (t, 2H, J = 6Hz),

3.73 (t, 4H, J = 5Hz), 3.84 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz),

 4.30 (d, 1H, J = 8Hz), 4.41 (dd, 1H, J = 7Hz, 10Hz), 4.89 (d, 1H, J = 8Hz),

 4.96 (s, 1H), 5.00 (s, lH), 5.24 (d, 1H, J = 10Hz), 5.32 (d, 1H, J = 10Hz),

 5.66 (d, 1H, J = 7Hz), 6.18 (t, 1H, J = 8Hz), 6.27 (d, 1H, J = 3.5Hz),

 6.36 (dd, 1H, J = 2Hz, 3.5Hz), 7.37 (s, 1H), 7.46 (t, 2H, J = 8Hz),

7.57 (t, 1H, J = 8Hz), 8. ll (d, 2H, J = 8Hz) Step 7: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxyhydrionyl] -4-dibutanoyl-4,10-dideacetyl -10-0- (2-morpholinoethyl) -paccatin ΙΠ

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a white solid.

Melting point: 135-137. C

 Ή-NMR (CDC / TMS) δ (ppm):

 0.99 (t, 3H, J = 7Hz), 1.19 (s, 3H), 1.21 (s, 3H), 1.35 (s, 9H), 1.68 (s, 3H),

1.78-1.84 (m, 3H), 1.93 (s, 3H), 2.30-2.38 (m, 2H), 2.53-2.68 (m, 9H),

 3.65-3.78 (m, 6H), 3.88 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz),

 4.26 (dd, 1H, J = 7H2, 10Hz), 4.30 (d, 1H, J = 8Hz), 4.70 (s, 1H),

 4.90 (d, 1H, J = 8Hz), 5.10 (s, 1H), 5.22 (d, 1H, J = 10Hz),

 5.31 (brd, 1H, J = 10Hz), 5.67 (d, 1H, J = 7Hz), 6.20 (t, 1H, J = 8Hz),

 6.35 (d, 1H, J = 3.5H2), 6.38 (dd, lH, J = 2Hz.3.5Hz), 7.42 (s, 1H),

 7.49 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz)

IR (KBr): 3456, 2972, 2944, 1720, 1604, 1498 cnf ¹

MS-FAB: 93 flower +)

Example 5

Step 1: 13-0-[(23S) -3- (tert-butoxycarbonylamino) -3- (2-furyl)- 2- (triisopropylsilyloxy) propionyl] -4,10-dideacetyl-10-O- [2- (N, N-getylamino) ethyl] -4-0-propionyl-7-7-0-triethylrunlylp Kachin III

 46.0 mg of the compound obtained in Step 5 of Example 3, 0.042 ml of getylamine and 0.024 ml of acetic acid were dissolved in 4 ml of ethanol, 26.0 mg of sodium cyanoborohydride was added, and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with a lip mouth form, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the obtained residue was purified by silica gel thin-layer chromatography (developing solvent; chloroform: methanol = 20: 1 (v / v)) to give 26.0 mg of the title compound as a colorless product As an amorphous solid.

Ή-NMR (CDCh / TMS) δ (ppm):

 0.50-0.65 (m, 6H), 0.94-1.01 (m, 30H), 1.18-1.23 (m, 6H), 1.34 (s, 9H), 1.36 (t, 3H, J = 7Hz), 1.68 (s, 3H ), 1.87-1.92 (m, 1H), 1.93 (s, 3H),

 2.26-2.39 (2H), 2.46-2.55 (m, 1H), 2.71-2.81 (m, 2H), 2.91 (br, 4H),

3.02 (br, 2H), 3.60-3.73 (m, 2H), 3.81 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz), 4.31 (d, lH, J = 8Hz), 4.44 (dd, 1H, J = 7Hz, 10Hz), 4.89 (d, 1H, J = 8Hz),

 4.95 (s, 1H), 4.98 (s, lH), 5.24-5.30 (m, 2H), 5.67 (d, 1H, J = 7Hz),

 6.20 (t, 1H, J = 8Hz), 6.27 (d, 1H, J = 3.5Hz), 6.37 (dd, 1H, J = 2Hz, 3.5Hz),

 7.39 (s, 1H), 7.47 (t, 2H, J = 8Hz), 7.57 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz) Step 2: 13-0-[( 2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-quinodium quinpropionyl] -4,10-dideacetyl-10-O- [2- (N, N-Jethylamino) ethyl] -4-0-Bropionirbaccatin 111

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a white solid.

Melting point: 128-132 ° C

Ή-NMR (CDCh / TMS) δ (ppm):

 1.10 (t, 6H, J = 7Hz), 1.20 (s, 3H), 1.22 (s, 3H), 1,29 (t, 3H, J = 7Hz),

 1.34 (s, 9H), 1.68 (s, 3H), 1.82-1.90 (m, 1H), 1.94 (s, 3H),

 2.28-2.36 (m, 2H), 2.51- 2.60 (ro, 1H), 2.70-2.80 (m, 6H),

2.84-2.90 (m, 2H), 3.70-3.73 (m, 1H), 3.85-3.89 (m, 2H), 4.17 (d, 1H, J = 8Hz), 4.30-4.33 (m, 2H), 4.71 (s, 1H), 4.91 (d, 1H, J = 8Hz), 5.19 (s, 1H),

 5.23 (d, 1H, J = 10Hz), 5.31 (brd, 1H, J = 10Hz), 5.68 (d, 1H, J = 7Hz),

 6.22 (t, 1H, J = 8Hz), 6.35 (d, 1H, J = 3.5Hz), 6.39 (dd, 1H, J = 2Hz, 3.5Hz),

7.43 (s, 1H), 7.48 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz) IR (KBr): 3456, 2980, 1720, 1496 cm " ¹

 MS-FAB: 91K H +)

Example 6

Step 1: 13—O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -4, 10-dideacetyl-4-1-0-propionyl-10-O- (2-thiomorpholinoethyl) -7-0-triethylsilylbactin III

 50.5 mg of the compound obtained in Step 5 of Example 3, 0.045 ml of thiomorpholine and 0.026 ml of acetic acid were dissolved in 4 ml of ethanol, and sodium cyanoborohydride 28.0 was added, followed by stirring at room temperature for 30 minutes. The mixture was diluted with black hole form, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the obtained residue was subjected to silica gel thin-layer chromatography (developing solvent; chloroform: methanol = 40:

Purification by Kv / v)) gave 43.5 mg of the title compound as a colorless amorphous solid.

■ H-NMR (CDC / TMS) <5 (ppm):

0.50-0.65 (m, 6H), 0.94-1.01 (m, 30H), 1.19 (s, 3H), 1.20 (s, 3H), 1.35 (s, 9H), 1.37 (t, 3H, J = 7Hz), 1.67 (s, 3H), 1.93 (s, 3H),

 2.31-2.39 (m, 2H), 2.45-2.53 (m, 1H), 2.67-2.81 (m, 9H), 2.84-2.86 (m, 4H),

3.59 (t, 2H, J = 6Hz), 3.82 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz),

 4.31 (d, 1H, J = 8Hz), 4.42 (dd, 1H, J = 7Hz, 10Hz), 4.89 (d, 1H, J = 8Hz),

 4.94 (s, lH), 4.99 (s, lH), 5.24-5.31 (m, 2H), 5.67 (d, 1H, J = 7Hz),

 6.20 (t, 1H, J = 8Hz), 6.27 (d, 1H, J = 3.5Hz), 6.37 (dd, 1H, J = 2Hz, 3.5Hz),

 7.39 (s, lH), 7.46 (t, 2H, J = 8 Hz), 7.57 (t, 1H, J = 8 Hz), 8. ll (d, 2H, J = 8 Hz) Step 2: 13-0-[( 2R, 3S)-3- (tert-butoxycarbonylamino) -3- (2-furyl)-

2-Hydroxypropionyl] -4,10-dideacetyl-4-1-O-propionyl -10-O

-(2-thiomorpholinoethyl) paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a white solid.

Contact point: 145-148 ° C

 Ή-NMR (CDCh / TMS) δ (ppm):

 1.19 (s, 3H), 1.21 (s, 3H), 1.29 (t, 3H, J = 7Hz), 1.34 (s, 9H), 1.67 (s, 3H), 1.78-1.85 (m, 1H), 1.92 ( s, 3H), 2.25-2.40 (m, 2H), 2.53-2.61 (m, 1H),

 2.66-2.72 (m, 8H), 2.78-2.90 (m, 4H), 3.61-3.67 (m, 1H), 3.72-3.78 (m, 1H),

3.86 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz), 4.27 (dd, 1H, J = 7Hz, 10Hz),

 4.31 (d, 1H, J = 8Hz), 4.71 (s, lH), 4.81 (d, 1H, J = 8Hz), 5.05 (s, 1H),

 5.22 (d, 1H, J = 10Hz), 5.31 (br, 1H, J = 10Hz), 5.68 (d, 1H, J = 7Hz),

 6.23 (t, 1H, J = 8Hz), 6.34 (d, 1H, J = 3.5Hz), 6.39 (dd, 1H, J = 2Hz, 3.5Hz),

7.43 (s, 1H), 7.48 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz) IR (Br): 3456, 2980, 2944, 2824, 1722, 1602, 1586, 1496 cm " ¹

MS-FAB: 941 (MH ⁺ ) Example 7

Step 1: 10-0-aryl-13-0-[(2R, 3S) -N- (tert-butynecarbonyl) -2,3-N, 0-isopropylidene-3-phenylphenyliserinyl] -10-deacetyl -7—0— Triethylilrilpackachin Π Ι

 150 mg of the compound obtained in Step 1 of Example 1 and (2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, 0-isopropylidene-3-phenylisoserine 207 rag Was dissolved in 4 ml of toluene. Cooled to C. Then, 146 mg of dicyclohexylcarpoimide was added, and the mixture was stirred for 15 minutes. Then, 26 mg of 4-dimethylaminopyridine was added, and the mixture was stirred with 80 and stirred for 15 minutes. After cooling, the mixture was diluted with ethyl acetate, washed with a 1N aqueous hydrochloric acid solution, a saturated aqueous sodium bicarbonate solution, and a saturated saline solution in that order, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin-layer chromatography (developing solvent; chloroform: acetone = 50: l (v / v)) to give 215 mg of the title compound as a colorless amorphous Obtained as a solid.

Ή-NMR (CDC / TMS) <5 (ppm): 0.50-0.62 (m, 6H), 0.94 (t, 9H, J = 7Hz), 1.10 (br-s, 9H), 1.22 (s, 6H),

 1.65 (s, 3H), 1.78 (s, 6H), 1.82 (s, 3H), 1.93 (s, 3H), 2.13-2.17 (m, 2H), 2.41-2.48 (m, 1H), 3.76 (d, 1H, J = 7Hz), 3.98-4.15 (m, 2H),

 4.09 (d, 1H, J = 8Hz), 4.23 (d, 1H, J = 8Hz), 4.36 (dd, 1H, J = 7Hz, 10Hz),

 4.47 (d, 1H, J = 7Hz), 4.86 (d, 1H, J = 8Hz), 4.97 (s, 1H), 5.10 (br, 1H),

 5.20 (d, 1H, J = llHz), 5.29 (dd, 1H, J = 1.5Hz, 11Hz), 5.62 (d, 1H.J = 7Hz),

 5.92-6.02 (m, 1H), 6.30 (t, 1H, J = 8Hz), 7.33-7.39 (m, 5H),

 7.50 (t, 2H, J = 8Hz), 7.61-7.65 (m, 1H), 8.03-8.05 (m, 2H)

Step 2: 13-0-[(2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, O-isobutypyridene-3-phenylisocerinyl] -10-deacetyl-10 -O-Formylmethyl -7-0-Triethylsilyl baccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 1 of Example 2 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) δ (ppm):

 0.51-0.59 (m, 6H), 0.95 (t, 9H, J = 7Hz), 1. ll (br-s, 9H), 1.23 (s, 6H),

 1.65 (s, 3H), 1.77 (s, 3H), 1.81 (s, 3H), 1.84 (s, 3H), 1.94 (s, 3H),

 2.14-2.17 (ι¾ 2H), 2.43-2.51 (m, 1H), 3.73 (d, 1H, J = 7Hz),

 4.10 (d, 1H, J = 8Hz), 4.17 (d, 2H, J = 2.5Hz), 4.24 (d, 1H, J = 8Hz),

 4.40 (dd, 1H, J = 7Hz, 10Hz), 4.46 (d, 1H, J = 7Hz), 4.86 (d, lH, J = 8Hz),

 5.05-5.13 (m, 1H), 5.ll (s, 1H) .5.62 (d, 1H, J = 7Hz), 6.28 (t, 1H, J = 8Hz),

7.34-7.40 (m, 5H), 7.49 (t, 2H, J = 8Hz), 7.62 (t, 1H, J = 8Hz),

 8.03 (d, 2H, J = 8Hz), 9.83 (s, 1H)

Step 3: 13-0-[(2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, 0-isopyridene-3-pyranylisoselinyl] -10-deacetyl-10 -0-(2-piperidinoethyl) -7-0—triethylsilylpaccatin III

52.4 mg of the compound obtained in the above step 2, 0.051 ml of piperidine and 0.030 ml of drunk acid were dissolved in 4 ml of ethanol, 33.0 mg of sodium cyanoborohydride was added, and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with black hole form, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the obtained residue was diluted with silica gel. Purification by layer chromatography (developing solvent; chloroform: methanol = 10: l (v / v)) gave 46.3 mg of the title compound as a colorless amorphous solid.

 Ή-NMR (CDC / T S) δ (ppm):

 0.50-0.60 (m, 6H), 0.94 (t, 9H, J = 7Hz), 1.10 (br-s, 9H), l, 19 (s, 3H),

 1.21 (s, 3H), 1.47 (br, 2H), 1.64 (s, 3H), 1.76-1.89 (m, 4H), 1.78 (s, 3H),

1.80 (s, 3H), 1.82 (s, 3H), 1.95 (s, 3H), 2.13-2.15 (m, 2H),

 2.40-2.48 (m, 1H), 2.58 (br, 4H), 2.73 (t, 2H, J = 6Hz), 3.63 (t, 2H, J = 6Hz),

3.76 (d, 1H, J = 7Hz), 4.09 (d, 1H, J = 8Hz), 4.23 (d, 1H, J = 8Hz),

 4.37 (dd, 1H, J = 7Hz, 10Hz), 4.46 (d, 1H, J = 7Hz), 4.86 (d, 1H, J = 8Hz),

 4.94 (s, lH), 5.05 (br, 1H), 5.61 (d, 1H, J = 7Hz), 6.28 (t, 1H, J = 8Hz),

 7.34- 7.38 (m, 5H), 7.49 (t, 2H, J = 8Hz), 7.63 (t, 1H, J = 8Hz), 8.03 (d, 2H, J = 8Hz) Step 4: 13-0 _ [(2R , 3S)-3- (tert-Butoxycarbonylamino) -2-hydroquine-3- 3-phenylpropionyl] -10-deacetyl -10-O- (2-piperidinoethyl)

 46.3 mg of the compound obtained in the above step 3 was dissolved in 4 ml of formic acid and reacted at room temperature for 80 minutes. The reaction solution was concentrated, the residue was diluted with chloroform, washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was dissolved in tetrahydrofuran (4 ml), di-tert-butyl dicarbonate (0.040 ml) was added, and the mixture was reacted at room temperature for 3 hours. After concentration, the obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: methanol: water = 8: 3: l (v / v), lower layer) to obtain 13.6 mg of the title compound as a white solid Obtained.

Melting point: 134-140. C

_{Ή-NMR (CDC1 3 / TMS} ) δ (ppm):

 1.19 (s, 3H), 1.20 (s, 3H), 1.34 (s, 9H), 1.46 (br, 2H), 1.67 (s, 3H),

 1.85-1.89 (m, 1H), 1.90 (s, 3H), 2.23-2.28 (m, 2H), 2.36 (s, 3H),

 2.45-2.73 (m, 7H), 3.74-3.84 (m, 3H), 4.17 (d, 1H, J = 8Hz),

 4.25 (dd, 1H, J = 7Hz, 10Hz), 4.29 (d, 1H, J = 8Hz), 4.62 (s, 1H),

 4.94 (d, lH, J = 8Hz), 5.20 (s, lH), 5.25 (br, 1H), 5.45 (br, 1H),

5.66 (d, 1H, J = 7Hz), 6.21 (t, 1H, J = 8Hz), 7.31-7.39 (m, 5H), 7.49 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz)

IR (KBr): 3440, 2940, 1722, 1604, 1496 cm " ¹

MS-FAB: 920 (MH ^÷ )

 Example 8

Step 1: 13-0-[(2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, 0-isopyridene 3-pyranylisoselinyl] -10-deacetyl-10 -O- [2- (N-pyrrolidino) ethyl] -7-0-triethylsilylpaccatin ΠΙ

 54.4 mg of the compound obtained in Step 2 of Example 7, 0.045 ml of pyrrolidine and 0.031 ml of acetic acid were dissolved in 4 ml of ethanol, 34.0 rog of sodium cyanoborohydride was added, and the mixture was stirred at room temperature for 1 hour. The mixture was diluted with black hole form, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the obtained residue was purified by silica gel thin brow chromatography (developing solvent; black form: methanol-10: 1 (v / v)) to give 34.6 mg of the title compound in colorless form As an amorphous solid.

Ή-NMR (CDC / TMS) δ (ppm):

 0.48-0.63 (m, 6H), 0.94 (t, 9H, J = 7Hz), 1.12 (br-s, 9H), 1.20 (s, 3H).

 1.21 (s, 3H), 1.64 (s, 3H), 1.77 (s, 3H), 1.81 (s, 3H), 1.85 (s, 3H),

 1.95 (s, 3H), 2.13-2.15 (m, 2H), 2.41-2.48 (m, 1H), 2.75 (br, 4H),

2.90 (t, 2H, J = 6Hz), 3.67 (t, 2H, J = 6Hz), 3.76 (d, 1H, J = 7Hz), 4.09 (d, 1H, J = 8Hz), 4.23 (d, 1H, J = 8Hz), 4.38 (dd, 1H, J = 7Hz, 10Hz),

 4.46 (d, 1H, J = 7Hz), 4.86 (d, 1H, J = 8Hz), 4.96 (s, lH), 5.08 (br, 1H),

 5.61 (d, 1H, J = 7Hz), 6.28 (t, 1H, J = 8Hz), 7.34-7.38 (m, 5H),

 7.48 (t, 2H, J = 8Hz), 7.62 (t, 1H, J = 8Hz), 8.03 (d, 2H, J = 8Hz)

Step 2: 13—0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- phenylpropionyl] -10-deacetyl-10-O- [2- (N —Virolizino) ethyl] Paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 4 of Example 7 to obtain the title compound as a white solid.

Melting point: 136-142 ° C

 Ή-NMR (CDC / TMS) δ (ppm):

 1.21 (s, 6H), 1.34 (s, 9H), 1.67 (s, 3H), 1.80 (br, 4H), 1.90 (s, 3H),

 2.23-2.28 (m, 2H), 2.36 (s, 3H), 2.45-2.53 (m, 1H), 2.70 (br, 4H),

 2.85 (br, 2H), 3.74-3.81 (m, 2H), 3.83 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz), 4.24 (dd, 1H, J = 7Hz, 10Hz) , 4.29 (d, 1H, J = 8Hz), 4.61 (s, lH),

 4.94 (d, 1H, J = 8Hz), 5,20 (s, lH), 5.25 (br, lH), 5.45 (br, 1H),

 5.66 (d, 1H, J = 7Hz), 6.21 (t, 1H, J = 8Hz), 7.31-7.0 (m, 5H),

 7.49 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz)

IR (KBr): 3448, 2976, 2820, 1852, 1720, 1634, 1604, 1588 cm " ¹

MS-FAB: 905 (MH ⁺ )

Example 9

Step 1: 10-0-aryl-10-deacetylbaccatin III

 292 mg of the compound obtained in Step 2 of Example 1 was dissolved in 5 ml of distilled pyridine and cooled to 0 ° C. Next, 1 ml of a hydrogen fluoride-pyridine solution was added dropwise at the same temperature. C After the completion of the dropwise addition, the mixture was heated to room temperature and stirred overnight. The reaction solution was diluted with ethyl acetate and washed with water. After washing with a saturated saline solution and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent; chloroform: acetone = 95: 5 (v / v)) to give 210 mg of the title compound.

 Ή-NMR (CDC / TMS) δ (ppm):

 1.07 (3H, s), 1.19 (3H, s), 1.68 (3H, s), 1.75-1.83 (1H, m),

 2.04 (3H, d, J = l. 5Hz), 2.27-2. 30 (1H, m), 2.29 (3H, s), 2.55- 2.63 (1H, m),

 3.95 (1H, d, J = 7.5Hz), 4.06 (1H, dd, J = 4.5Hz, 7.5Hz), 4.16 (1H, d, J = 8.5Hz),

 4.2K1H, dd, J = 5Hz, 8.5Hz), 4.24-4.31 (1H, m), 4.31 (1H, d, J = 8.5Hz),

 4.85-4.91 (1H, m), 4.98 (1H, d, J = 8Hz), 5.09 (1H, s),

 5.23 (1H, dd, J = l.5Hz, 9.5Hz), 5.33 (1H, dd, J = l.5Hz, 15.5Hz),

 5.64 (1H, d, J = 7.5Hz), 5.91-6.02 (1H, m), 7.48 (2H, t, J = 7.5Hz),

 7.61 (1H, t, J = 7.5Hz), 8.11 (2H, d, J = 7.5Hz).

Process 2: 10-0-aryl-10-deacetyl-7-doxybactin I I I

20 mg of sodium hydride (oil suspension (oil / suspension) (w / w)) was suspended in tetrahydrofuran, and 219 mg of the compound obtained in Step 1 was added to 2 ml of tetrahydrofuran. The solution dissolved in was added dropwise at -45. After stirring at the same temperature for 10 minutes, 0.03 ml of carbon disulfide and 0.03 ml of methyl iodide were added, the temperature was raised to 0 ° C, and the mixture was stirred overnight. After adding a saturated aqueous solution of ammonium chloride to the reaction solution, the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent; liquid form: methanol: 97: 3 (v / v)) to give 10-O-aryl-10-deacetyl-7-0-. [(Methylthio) thiocarbonyl] paccatin 145 145 mg was obtained. This compound was dissolved in 2 ml of degassed dioxane under a nitrogen atmosphere, and 10 nrn of 2,2'-azobis (isobutyronitrile) was dissolved. And 0.25 ml of triptyltin hydride. The mixture was stirred at C overnight. After cooling the reaction solution, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 2: l (v / v)). 63 mg of the title compound were obtained.

Ή-NMR (CDCh / TMS) δ (ppm):

 1.06 (3H, s), 1.15 (3H, s), 1.22-1.72 (3H, m), 1.74C3H, s),

 1.90-2.10 (1H, m), 2.02 (3H, s), 2.19-2.37 (2H, m), 2.28 (3H, s),

 3.86 (1H, d, J = 7.5Hz), 4.05-4.17 (2H, m), 4.20 (1H, d, J = 8.5Hz),

 4.31 (1H, d, J = 8.5Hz), 4.81-4.90 (1H, br), 4.96 (1H, d, J = 10Hz), 5.07 (1H, s), 5.22 (1H, d, J = llHz), 5.3K1H, d, J = 17Hz), 5.62 (1H, d, J = 7.5Hz),

 5.91-6.01 (1H, m), 7.48 (2H, t, J = 7.5Hz), 7.60 (1H, t, J = 7.5Hz),

 8.12 (2H, d, J = 7.5Hz)

Step 3: 10-0-aryl-13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10- Decetyl -7-Doxypaccatin III

 96 mg of sodium hydride (about 60X oil suspension (w / w)) is suspended in 2 ml of tetrahydrofuran, and the compound 46 obtained in the above step 2 is dissolved in 1 ml of dry tetrahydrofuran and added at 0 ° C. Was. Then, 61 mg of (3R, 4S) -1- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyloxy) -4-phenylazetidin-2-one was added, and 3 mg was added at the same temperature. Stirred for hours. After adding a saturated ammonium chloride solution to the reaction solution, the mixture was extracted with ethyl acetate. The extract was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-layer chromatography (developing solvent; hexane: ethyl acetate = 2: 1 (v / v)) to obtain 35 rag of the title compound.

Ή-NMR (CDCh / TMS) δ (ppm):

 -0.12 (6H, s), 0.75 (9H, s), 1.19 (3H, s), 1.23 (3H, s), 1.26 (6H, s),

 1.29 (9H, s), 1.38-1.48C1H, m), 1.52-1.58 (1H, m), 1.76C3H, s),

 1.86 (3H, s), 1.89-2.02 (1H, m), 2.08-2.28 (2H, m), 2.35-2.47 (lH, m),

2.55 (3H, s), 3.80 (1H, d, J = 7.5Hz), 4.09-4.16 (2H, m), 4.23 (1H, d, J = 8.5Hz), 4.33C1H, d, J = 9Hz), 4.5K1H, br-s), 4.96 (1H, d, J = 8.5Hz), 5.03 (1H, s),

5.22 (1H, d, J = 10.5Hz), 5.28-5.36 (1H, m), 5.31 (1H, d, J = 19Hz),

 5.41-5.47 (1H, m), 5.68 (1H, d, J = 7.5Hz), 5.90-5.99 (1H, m),

 6.29-6. 35 (1H, m), 7.26-7.30 (5H, m), 7.49 (2H, t, J = 7.5Hz),

 7.58C1H, t, J = 7.5Hz), 8.13 (2H, d, J = 7.5Hz)

Step 4: 10-0-aryl-13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -2-hydroxy-3--3-phenylpropionyl] -10-deacetyl-7 Deoxypaccachin 1 1 1

 35 mg of the compound obtained in the above step 3 was dissolved in 2 ml of distilled pyridine, and 0.4 ml of hydrogen fluoride-pyridine was added at 0 ° C. After completion of the dropwise addition, the mixture was heated to room temperature and stirred for one night. The reaction solution was diluted with water and extracted with ethyl acetate. The extract was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-layer chromatography (eluent: developing solvent: ethyl form: acetone = 95: 5 (v / v)) to give 21 mg of the title compound.

Ή-NMR (CDC / TMS) δ (ppm):

 1.19 (3H, s), 1.2K3H, s), 1.33 (9H, s), 1.51-1.56 (1H, m),

 1. 64-1.6.67 (1H, m), 1.75 (3H, s), 1.82 (3H, s), 1.89-2.04 (2H, m),

 2.19-2.27 (1H, m), 2.31.40 (1H, m), 2.38 (3H, s), 3.36 (1H, br-s),

 3.77 (1H, d, J = 7.5Hz), 4.10-4.13 (2H, m), 4.21 (1H, d, J = 8.5Hz),

 4.31 (1H, d, J = 8.5Hz), 4.6K1H, brs), 4.93 (1H, d, J = 8.5Hz), 5.02 (1H, s), 5.23 ( 1H, dd, J = l. 5Hz, 9Hz), 5.23-5. 29 (1H, m),

 5.3K1H, dd, J = l.5Hz, 15.5Hz), 5.39 (1H, d, J = 9.5Hz), 5.67 (1H, d, J = 7.5Hz), 5.90 -6. 00 (1H, m), 6.22-6. 27 (1H, m), 7.25-7. 40 (5H, m),

 7.50 (2H, t, J = 7.5Hz), 7.61 (1H, t, J = 7.5Hz), 8.13 (2H, d, J = 7.5Hz)

Example 10

 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl-10-O- (2 -Morpholinoethyl) -4- 0—propionylbaccatin III · methanesulfonate

59 mg of the compound obtained in Step 7 of Example 3 was added to 2 ml of t-butanol and 1.5 m of water. Dissolved in 1 and cooled to about 5 ° C. Next, methanesulfonic acid (0.02 M solution, 3.1 ml) per 1 S was added dropwise, and the mixture was stirred at the same temperature for 2 minutes. The resulting solution was passed through a Millipore filter and freeze-dried to obtain 51 mg of the title compound as a white solid.

 Melting point: 157-161 ° C

 Ή-NMR (CDCh / TS) 5 (ppm):

 1.17 (s, 3H), 1.20 (s, 3H), 1.27 (t, 3H, J = 7Hz), 1.34 (s, 9H), 1.67 (s, 3H), 1 85-1. 92 (m, IH), 2.04 (s, 3H), 2.21-2.40 (m, 2H), 2.45-2.56 (m, IH),

 2.65-2.70 (m, 2H), 2.78 (s, 3H), 3.04 (m, 4H), 3.29 (br, 2H),

 3.81 (d, IH, J = 7Hz), 3.92-4.10 (m, 6H), 4.16 (d, IH, J = 8Hz),

 4.30 (d, IH, J = 8Hz), 4.35 (dd, IH, J = 7H2, 10Hz), 4.70 (s, IH),

 4.91 (d, IH, J = 8Hz), 5.25-5.30 (m, 2H), 5.54 (s, 1H), 5.67 (d, IH, J = 7Hz),

6.21 (t, 1H, J = 8Hz), 6.34 (d, 1H, J = 3.5Hz), 6.37 (dd, IH, J = 2Hz, 3.5H2),

 7.43 (s, IH), 7.48 (t, 2H, J = 8Hz), 7.60 (t, IH, J = 8Hz), 8.12 (d, 2H, J = 8Hz) IR (KBr ): 3432, 2968, 2940, 1980, 1720, 1602, 1584 cnf '

MS-FAB: 925 (H ⁺ )

Example 1 1

Process 2

Step 1: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3_fuunylpropionyl] -10-deacetyl-7- Deoxy -10-O- (2-morpholinoethyl) paccatin III

 The compound obtained in Step 3 of Example 9 was reacted in the same manner as in Step 1 of Example 2 and then reacted in the same manner as in Step 2 of Example 2 to obtain the title compound.

 Ή-NMR (CDCh / TMS) δ (ppm):

 -0.32 (3H, s), -0.ll (3H, s), 0.75 (9H, s), 1.16 (3H, s), 1.23C3H, s),

 1.29 (9H, s), 1.52-1.82 (2H, m), 1.75 (3H, s), 1.89 (3H, s),

 1.95- 2.46 (4H, m), 2.55 (3H, s), 2.46-2.66 (4H, m), 2.65-2.71 (2H, m),

 3.66-3.78 (6H, m), 3.80 (1H, d, J = 7Hz), 4.23 (1H, d, J = 8Hz),

 4.33 (1H, d, J = 8Hz), 4.52 (1H, s), 4.96 (1H, d, J = 9Hz), 5.04 (1H, s),

 5.29-5.35 (1H, m), 5.40-5.45 (1H, m), 5.67 (1H, d, J = 7Hz), 6.3K1H, m),

 7.27-7.46 (5H, m), 7.49 (2H, t, J = 8Hz), 7.58 (1H, t, J = 7Hz),

 8.13 (2H, d, J = 8Hz).

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-7-deoxy-10-O_ ( 2-Morpholinethyl) Paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 9 to obtain the title compound.

 Ή-NMR (CDCh / TMS) δ (ppm):

 1.17 (3H, s), 1.2K3H, s), 1.33 (9H, s), 1.50-1.74 (2H, m), 1.74 (3H, s),

 1.86C3H, s), 1.90- 2.41 (4H, m), 2.38 (3H, s), 2.50-2.65 (4H, m),

 2.68 (2H, m), 3.61-3.76 (6H, m), 3.77 (1H, d, J = 7Hz), 4.21 (1H, d, J = 8Hz),

 4.3K1H, d, J = 8Hz), 4.46 (lH, s), 4.93 (1H, d, J = 8Hz), 5.05C1H, s),

 5.24-5.30 (1H, m), 5.30-5.35 (1H, m), 5.66 (1H, d, J = 7Hz), 6.22 (lH, m),

 7.27-7.41 (5H, m), 7.50 (2H, t, J = 8Hz), 7.59 (1H, t, J = 8Hz),

8.13 (2H, d, J = 8Hz). Example 1 2

Step 1: 10-0-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3-phenyl-2- (triethylsilyloxy) propionyl] -4,10- Didacetyl -4-0- propionyl -7- 0- triethylsilyl paccatin III

 The compound obtained in Step 3 of Example 3 and (3R, 4S) -l-tert- (butoxycarbonyl) -4-phenyl-3- (triethylsilyloxy) azetidin-2-one were treated with Example 3 The reaction was carried out in the same manner as in Step 4, to obtain the title compound as a colorless amorphous solid.

_{! H-NMR (CDC1 3 /} TMS) δ (ppm):

 0.33-0.49 (m, 6H), 0.52-0.62 (m, 6H), 0.79 (t, 9H, J = 8Hz), 0.96 (t, 9H, J = 8Hz), 1.24 (s, 6H), 1.34 (s , 9H), 1.38 (t, 3H, J = 7Hz), 1.69 (s, 3H), 1.90 (s, 3H),

1.88-1.92 (m, 1H), 2.18-2.27 (m, 1H), 2.33-2.41 (m, 1H), 2.45-2.52 (m, 1H), 2.73-2.85 (m, 2H), 3.83 (d, 1H , J = 7Hz), 4.05 (dq, 2H, J = 5Hz, 12.5Hz), 4.20 (d, 1H, J = 8Hz), 4.33 (d, 1H, J = 8Hz), 4.43 (dd, 1H, J = 7Hz, 10Hz), 4.54 (s, 1H), 4.90 (d, 1H, J = 8Hz), 4.99 (s, 1H), 5.20 (d, 1H, J = 10.5Hz),

 5.23 (d, 1H, J = 10Hz), 5.32 (dd, 1H, J = 1.5Hz, 17Hz), 5.47 (d, 1H, J = 10Hz),

 5.69 (d, 1H, J = 7Hz), 5.94-6.02 (m, 1H), 6.26 (t, 1H, J = 8Hz), 7.28-7.40 (m, 5H), 7.48 (t, 2H, J = 8Hz) , 7.59 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz)

Step 2: 13-0 _ [(2R, 3S) -3- (tert-butoxycarbonylamino) -3-phenyl-2- (triethylsilyloxy) propionyl] -4,10-didecetyl-4-0- Propionyl -10-0- (2-thiomorpholinoethyl) -7-0-triethylsilylpaccatin III The compound obtained in the above step 1 was reacted in the same manner as in the step 1 of the example 2. The reaction was carried out using thiomorpholine in place of morpholine 2 to give the title compound as a colorless amorphous solid.

 ■ H-N RCCDCh / TMS) δ (ppm):

 0.34-0.49 (m, 6H), 0.52-0.63 (m, 6H), 0.79 (t, 9H, J = 8Hz), 0.96 (t, 9H, J = 8Hz), 1.21 (s, 3H), 1.23 (s , 3H), 1.33 (s, 9H), 1.38 (t, 3H, J = 7Hz), 1.67 (s, 3H),

1.91 (s, 3H), 1.89-1.94 (m, 1H), 2.17-2.24 (m, 1H), 2.32-2.40 (m, 1H),

 2.45-2.52 (m, 1H), 2.67-2.76 (m, 8H), 2.82-2.90 (m, 4H), 3.59 (t, 2H, J = 6Hz),

3.82 (d, 1H, J = 7Hz), 4.19 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz),

 4.43 (dd, 1H, J = 7Hz, lOHz), 4.53 (s, lH), 4.90 (d, 1H, J = 8Hz), 4.93 (s, 1H),

 5.22 (d, 1H, J = 10Hz), 5.46 (d, 1H, J = 10Hz), 5.68 (d, 1H, J = 7Hz),

6.25 (t, 1H, J = 8Hz), 7.28-7.40 (m, 5H), 7.48 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz)

Step 3: 13-0-[(2R.3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4,10-dideacetyl-4-4-0-propionyl- 10-O- (2-thiomorpholinoethyl) paccatin 111

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a white solid.

Contact point: 142-146 ° C

■ H-NMRCCDCh / TMS) «5 (ppm):

1.19 (s, 3H), 1.21 (t, 3H, J = 7Hz), 1.22 (s, 3H), 1.34 (s, 9H), 1.67 (s, 3H), 1.76-1.88 (m, 1H), 1.89 (s, 3H), 2.29 (m, 2H), 2.53-2.59 (m, 3H),

 2.64-2.78 (m, 6H), 2.79-2.89 (m, 4H), 3.62-3.67 (m, 1H), 3.71-3.85 (m, 1H),

3.84 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz), 4.26 (dd, 1H, J = 7Hz, 10Hz),

 4.31 (d, 1H, J = 8Hz), 4.62 (s, 1H), 4.89 (d, 1H, J = 8Hz), 5.05 (s, 1H),

 5.23 (br, lH), 5.32 (d, 1H, J = 9Hz), 5.67 (d, 1H, J = 7Hz), 6.21 (t, 1H, J = 8Hz),

7.31-7.42 (m, 5H), 7.50 (t, 2H, J = 8Hz), 7.62 (t, 1H. J = 8Hz), 8.12 (d, 2H, J = 8Hz) IR (KBr): 3456, 3068, 2980, 2944, 2820, 1968, 1818, 1722, 1604,

 1584 cnf '

MS-FAB: 951 (MH ^÷ )

 Example 13

Step 1: 10-0-aryl-10-deacetyl-13-0- (2,2,2-trichloromouth ethoxycarbonyl) -7-0-triethylsilylpaccatin ΙΠ

Dissolve 200 mg of the compound obtained in Step 1 of Example 1 in 4 ml of pyridine, and add chloroform. 0.22 ml of 2,2,2-trichloroethyl acid was added, and the mixture was heated and stirred at 80 ° C for 30 minutes. After cooling, the mixture was poured into ice water, extracted with ethyl acetate, and washed with 1N hydrochloric acid, a saturated aqueous solution of sodium bicarbonate, and a saturated saline solution in this order. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was developed and purified by silica gel thin layer chromatography (developing solvent; chloroform: acetone = 40: 1 (v / v)) to obtain 220 mg of the title compound as a colorless amorphous solid. ■ H-NMRCCDCh / TMS) δ (ppm):

 0.50-0.64 (m, 6H), 0.95 (t, 9H, J = 8Hz), 1.14 (s, 3H), 1.23 (s, 3H), 1.67 (s, 3H), 1.85- 1.92 (m, 1H), 2.00 (s, 3H), 2.37 (d, 2H, J = 8Hz), 2.39 (s, 3H),

2.45- 2.53 (m, 1H), 3.87 (d, 1H, J = 7Hz), 4.05-4.ll (m, 2H),

4.13 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

 4.43 (dd, 1H, J = 7Hz, 10Hz) 4.84 and 4.89 (each d, each 1H, J = 12Hz),

 4.95 (d, 1H, J = 8Hz), 5.02 (s, lH), 5.21 (dd, 1H, J = l.5Hz, 10.5Hz),

 5.32 (dd, 1H, J = 1.5Hz, 17Hz), 5.63 (d, 1H, J = 7Hz), 5.93-6.00 (m, 1H),

 6.02 (t, 1H, J = 8Hz), 7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.07-8.09 (m, 2H) Step 2: 10-deacetyl -10- O- (2-thiomorpholinoethyl) -13- 0- (2,2,2-trichloroethoxycarbonyl) -7-0- triethylsilylpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 1 of Example 2, and then reacted in the same manner as in Step 2 of Example 2 using thiomorpholine instead of morpholine to give the title compound as a colorless amorphous solid As obtained.

"H-NMRCCDCh / TMS) δ (ppm):

 0.49- 0.64 On, 6H), 0.95 (t, 9H, J = 8Hz), 1.13 (s, 3H), 1.20 (s, 3H), 1.67 (s, 3H), 1.85-1.99 (m, 1H), 2.01 (s, 3H), 2.33-2.39 (m, 2H), 2.38 (s, 3H),

 2.45-2.54 (m, 1H), 2.66-2.79 (m, 6H) 2.82-2.85 (m, 4H), 3.53-3.62 (m, 1H),

3.64- 3.68 (m, 1H), 3.86 (d, 1H, J = 7Hz), 4.12 (d, 1H, J = 8Hz), 4.15 (s, 1H),

4.31 (d, 1H, J = 8Hz), 4.44 (dd, 1H, J = 7Hz, 10Hz),

 4.83 and 4.88 (each d, 1H each, J = 12Hz), 4.94 (d, 1H, J = 8Hz), 4.97 (s, 1H),

5.62 (d, 1H, J = 7Hz), 6.01 (t, 1H, J = 8Hz), 7.48 (t, 2H, J = 8Hz),

 7.61 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz)

Step 3: 10-Deacetyl -10-O- (2-thiomorpholinoethyl)-7-0- Triethylsi Lilpacchin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 2 of Example 3 to obtain the title compound as a colorless amorphous solid.

'H-NMR (CDCh / TMS) δ (ppm):

0.50-0.65 (m, 6H), 0.96 (t, 9H, J = 8Hz), 1.05 (s, 3H), 1.17 (s, 3H), 1.66 (s, 3H), 1.85-1.97 (m, 1H), 2.08 (s, 3H), 2.26 (d, 2H, J = 9Hz), 2.28 (s, 3H),

 2.45-2.53 (m, 2H), 2.66-2.74 (m, 6H), 2.83-2.85 (m, 4H), 3.54-3.60 (m, 1H ),

3.62-3. 68 (m, 1H), 3.87 (d, 1H, J = 7Hz), 4.14 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz) ),

4.43 (dd, 1H, J = 7Hz, 10Hz), 4.87 (br, 1H), 4.96 (d, 1H, J = 8Hz), 4.97 (s, 1H), 5.60 ( d, 1H, J = 7Hz), 7.47 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz) Step 4: 13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3-phenyl-2- (triethylsilylloquine) propionyl] -10-deacetyl-10-O- (2-thiomorpho Linoethyl) -7-0- Triethylsilyl paccatin III

 The compound obtained in the above Step 3 and (3R, 4S) -1- (tert-butoxycarbonyl) -4-phenyl-3- (triethylsilyloxy) azetidin-2-one were treated with Step 4 of Example 3. The same reaction was performed to obtain the title compound as a colorless amorphous solid.

'H-NMR (CDCh / TMS) δ (ppm):

 0.33-0.48 (m, 6H), 0.52-0.62 (m, 6H), 0.79 (t, 9H, J = 8Hz), 0.96 (t, 9H, J = 8Hz ), 1.20 (s, 3H), 1.23 (s, 3H), 1.32 (s, 9H), 1.68 (s, 3H), 1.91 (s, 3H),

1.89-1.94 (m, 1H), 2.15-2.22 (m, 1H), 2.31-2.40 (m, 1H), 2.44-2.51 (m, 1H ),

2.52 (s, 3H), 2.67-2. 73 (m, 6H), 2. 84-2.86 (m, 4H), 3.58-3 · 60 (m, 2H),

 3.83 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

 4.41 (dd, 1H, J = 7Hz, 10Hz), 4.56 (s, lH), 4.93 (s, 1H), 4.94 (d, 1H, J = 8Hz),

 5.30 (br, 1H), 5.46 (br, 1H), 5.67 (d, 1H, J = 7Hz), 6.30 (t, 1H, J = 8Hz),

7.28-7.46 (m, 5H), 7.48 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz) ) Step 5: 13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-10-O- (2 -Thiomorpholinoethyl) paccatin III

The compound obtained in Step 4 above was reacted in the same manner as in Step 7 of Example 3 to remove the title compound. Obtained as a colored solid.

Melting point: 152-156. C

■ H-NMRCCDC / TMS) δ (ppm):

 1.19 (s, 3H), 1.21 (s, 3H), 1.35 (s, 9H), 1.68 (s, 3H), 1.85-1.92 (m, 1H),

1.88 (s, 3H), 2.22-2.27 (m, 2H), 2.37 (s, 3H), 2.52-2.58 (m, 1H),

 2.67-2.73 (m, 6H), 2.82-2.90 (m, 4H), 3.63- 3.66 On, IH), 3.75-3.78 (m, IH),

3.85 (d, IH, J = 7Hz), 4.17 (d, 1H, J = 8Hz), 4.22 (dd, IH, J = 7Hz, 10Hz),

 4.30 (d, IH, J = 8Hz), 4.62 (s, IH), 4.94 (d, IH, J = 8Hz), 5.06 (s, IH),

 5.25 (br, 1H), 5.39 (d, IH, J = 10Hz), 5.66 (d, IH, J = 7Hz), 6.22 (t, 1H, J = 8Hz), 7.31-7.42 (m, 5H), 7.49 (t, 2H, J = 8Hz), 7.61 (t, IH, J = 8Hz), 8.10 (d, 2H, J = 8Hz) IR (KBr): 3456, 3068, 2980, 2944, 2820, 1968, 1818, 1722, 1604,

1584 cm " ¹

MS-FAB: 937 (MH ⁺ )

Example 14

Step 1: 10-0-aryl-13_0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl]- 10- Dasechi Le -7- 0- Triethylsilyl paccatin III

 The compound obtained in Step 1 of Example 1 and (3R.4S) -tri (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyloxy) -4-phenylazetidine-2-one Was reacted in the same manner as in Step 4 of Example 3 to obtain the title compound as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 -0.30 (s, 3H), -0.10 (s, 3H), 0.54-0.6 Km, 6H), 0.76 (s, 9H),

0.96 (t, 9H, J = 8Hz), 1.24 (s, 6H), 1.32 (s, 9H), 1.69 (s, 3H), 1.90 (s, 3H), 1.89-1.94 (m, 1H), 2.14- 2.21 (m, 1H), 2.32-2.42 (m, 1H), 2.45-2.54 (m, 1H), 2.56 (s, 3H), 3.85 (d, 1H, J = 7Hz), 4.00-4.10 (m, 2H ), 4.19 (d, 1H, J = 8Hz),

4.31 (d, 1H, J = 8Hz), 4.41 (dd, 1H, J = 7Hz, 10Hz), 4.54 (s, 1H),

 4.95 (d, 1H, J = 8Hz), 4.98 (s, 1H), 5.20 (d, 1H, J = 12Hz),

 5.32 (dd, 1H, J = 2Hz, 17.5Hz), 5.33 (d, 1H, J = 10Hz), 5.42 (d, 1H, J = 10Hz),

 5.68 (d, 1H, J = 7Hz), 5.93-6.01 (m, 1H), 6.34 (t, 1H, J = 8Hz), 7.28-7.39 (m, 5H), 7.47 (t, 2H, J = 8Hz) 7.59 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz)

Step 2: 10-0-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (terbutyldimethylsilyloxy) -3-phenylpropionyl] -10 -Dessic Rubaccatin III

 198 mg of the compound obtained in the above step 1 was dissolved in 4 ml of acetonitrile and cooled to -10 ° C. Next, 0.050 ml of 12N hydrochloric acid was added dropwise and stirred for 1 hour. A saturated sodium bicarbonate aqueous solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was developed and purified by silica gel thin-layer chromatography (developing solvent; chloroform: methanol = 40: 1 (v / v)) to give 136 mg of the title compound as a colorless amorphous Obtained as a solid.

■ H-NMRCCDCh / TMS) δ (ppm):

-0.30 (s, 3H), -0.10 (s, 3H), 0.75 (s, 9H), 1.22 (s, 3H), 1.24 (s, 3H),

 1.31 (s, 9H), 1.70 (s, 3H), 1.79-1.82 (m, 1H), 1.88 (s, 3H), 2.17 (m, 1H),

2.35-2.41 (m, 1H), 2.66 (s, 3H), 2.66-2.81 (m, 1H), 3.90 (d, 1H, J = 7Hz),

4.04-4.09 (m, 1H), 4.16-4.23 (m, 3H), 4.31 (d, lH, J = 8Hz), 4.52 (s, 1H),

4.97 (d, 1H, J = 8Hz), 5.04 (s, 1H), 5.21 (d, 1H, J = 12Hz), 5.28 (br, 1H), 5.31 (d, 1H, J = 17Hz), 5.53 (br, 1H), 5.70 (d, 1H, J = 7Hz), 5.90-5.98 (m, 1H),

6.32 (t, 1H, J = 8Hz), 7.27-7.34 (m, 5H), 7.48 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.ll (d, 2H, (J = 8Hz)

Step 3: 10-0-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10- Deacetyl-7- 0- Trifluoromethanesulfonyl baccatin III

136 mg of the compound obtained in the above step 2 was dissolved in 3 ml of methylene chloride and 3 ml of pyridine, and cooled to -30 ° C. Next, 0.059 ml of trifluoromethanesulfonic anhydride was added dropwise, and the temperature was raised to room temperature over 3 hours. A saturated aqueous solution of ammonium chloride was added, extracted with ethyl acetate, and washed with a 1N aqueous solution of sodium hydrogen sulfate and a saturated aqueous solution of sodium bicarbonate in this order. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel thin-layer chromatography (developing solvent: acetic Echiru: hexane = 1: 4 (v / v )) c to afford the title compound 123 mg expand purified as an amorphous solid pale yellow _{'H ^ MR (CDC1 3 /} TMS) δ (ppm):

-0.31 (s, 3H), -0.12 (s, 3H), 0.76 (s, 9H), 1.24 (s, 3H), 1.25 (s, 3H),

 1.33 (s, 9H), 1.89 (s, 3H), 1.93 (s, 3H), 2.17-2.28 (m, 2H), 2.35-2.41 (m, 1H), 2.58 (s, 3H), 2.78-2.85 ( m, 1H), 3.98 (d, 1H, J = 7Hz), 4.06-4.21 (m, 4H),

 4.34 (d, 1H, J = 8Hz), 4.53 (s, lH), 4.93 (d, 1H, J = 8Hz), 5.18 (s, 1H),

 5.20 (d, 1H, J = 12Hz), 5.28 (br, 1H), 5.31 (d, 1H, J = 17Hz), 5.42-5.49 (m, 2H), 5.72 (d, 1H, J = 7Hz), 5.91 -6.01 (m, 1H), 6.32 (t, 1H, J = 8Hz), 7.27-7.40 (m, 5H),

7.49 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz)

Step 4: 10-0-aryl-13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-7-deoxy-7,8; 9-methanobaccatin III

123 mg of the compound obtained in the above step 3 was dissolved in 3 ml of 1,4-dioxane, a solution of 100 mg of sodium azide dissolved in 0.60 ml of water was added, and the mixture was heated under a nitrogen atmosphere for 1 hour. After cooling, the mixture was diluted with ethyl acetate, and washed with water and saturated saline in this order. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin eye chromatography (developing solvent: ethyl acetate: hexane di 1: 2 (v / v)). Thus, 58.6 mg of the title compound was obtained as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 -0.33 (s, 3H),-0.12 (s, 3H), 0.74 (s, 9H), 1.25 (s, 9H), 1.29 (s, 3H),

1.30 (s, 3H), 1.66-1.69 (m, 1H), 1.84 (s, 3H), 2.10-2.19 (m, 2H),

2.28-2.31 (m, 1H), 2.41-2.47 (m, 2H), 2.53 (s, 3H), 4.05 (d, 1H, J = 9Hz),

4.11-4.14 (m, 2H), 4.32 (d, 1H, J = 8Hz), 4.51 (s, lH), 4.75 (d, 1H, J = 3.5Hz),

4.83 (s, lH), 5.21 (dd, 1H, J = 1.5Hz, 10Hz), 5.30-5.35 (m, 2H), 5.40 (br, 1H),

5.68 (d, 1H, J = 7Hz), 5.91-6.01 (m, 1H), 6.36 (t, 1H, J = 8Hz), 7.26- 7.39 (m, 5H), 7.48 (t, 2H, J = 8Hz) , 7.58 (t, 1H, J = 8Hz), 8.14 (d, 2H, J = 8Hz)

Step 5: 13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -2- (tert-butyldimethylsilyloxy) _3-phenylpropionyl] -10-deacetyl-7- Deoxy-Ίβ, Ββ-methano-10-Ο- (2-thiomorpholinoethyl) paccatin III

 The compound obtained in the above Step 4 was reversed in the same manner as in Step 1 of Example 2, and then reacted in the same manner as in Step 2 of Example 2 using thiomorpholine instead of morpholine to convert the title compound to a colorless amorphous substance. Obtained as a crystalline solid.

■ H-NMRCCDC / TMS) δ (ppm):

 -0.32 (s, 3H), -0. Ll (s, 3H), 0.74 (s, 9H), 1.25 (s, 3H), 1.26 (s, 9H),

1.29 (s, 3H), 1.61-1.64 (m, 1H), 1.87 (s, 3H), 2.10-2.18 (m, 2H),

2.26-2.31 (m, 1H), 2.36-2.47 (m, 2H), 2.52 (s, 3H), 2.64-2.72 (m, 6H),

2.82-2.85 (m, 4H), 3.61-3.74 (m, 2H), 4.05 (d, 1H, J = 9Hz), 4.10 (d, 1H, J = 8Hz),

4.31 (d, 1H, J = 8Hz), 4.51 (s, lH), 4.75 (d, 1H, J = 3.5Hz), 4.83 (s, 1H),

 5.32 (d, 1H, J = 10Hz), 5.44 (d, 1H, J = 10Hz), 5.66 (d, 1H, J = 7Hz),

 6.35 (t, 1H, J = 8Hz), 7.26-7.39 (m, 5H), 7.48 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 8.14 (d, 2H, J = 8Hz)

Step 6: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-fuunylpropionyl] -10-deacetyl-7-deoxy-7; 5, 85- methano-10-O- (2-thiomorpholinoethyl) paccatin III

The compound obtained in the above Step 5 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a colorless solid. Melting point: 139-144 ° C

_{'Η- NMR (CDC1 3 / TMS} ) δ (ppm):

 1.22 (s, 3H), 1.27 (s, 9H), 1.29 (s, 3H), 1.61-1.64 (m, IH), 1.85 (s, 3H), 2.13- 2.40 (m, 5H), 2.37 (s, 3H), 2.66-2.72 (m, 6H), 2.81-2.84 (m, 4H),

3.60-3.75 (m, 2H), 4.03 (d, IH, J = 8Hz), 4.08 (d, IH, J = 7Hz), 4.30 (d, IH, J = 8Hz), 4.61 (s, IH), 4.72 (d, IH, J = 3.5Hz), 4.83 (s, 1H), 5.30 (br, 1H),

5.35 (d, lH, J = 10 Hz), 5.73 (d, IH, J = 7 Hz), 6.29 (t, IH, J = 8 Hz),

7.29-7.42 (m, 5H), 7.50 (t, 2H, J = 8Hz), 7.61 (t, IH, J = 8Hz), 8.14 (d, 2H, J = 8Hz) IR (KBr): 3452, 3068, 2976, 2936, 2820, 2100, 1866, 1716, 1602,

1586 cm " ¹

MS-FAB: 919 (10 MH)

Example 15

Step 1: 10-O-aryl-4,10-dideacetyl-4-0-propionylbaccatin III The compound obtained in Step 3 of Example 3 is reacted in the same manner as in Step 7 of Example 3 to give the compound. Obtained as a colorless amorphous solid.

'H-NMRCCDCls / T S) δ (ppm):

1.07 (s, 3H), 1.19 (s, 3H), 1.23 (t, 3H, J = 7 Hz), 1.68 (s, 3H), 1.76-1.83 (m, 1H), 1.95 (d, 1H, J = 5 Hz) ), 2.04 (s, 3H), 2.26-2.28 (m, 2H), 2.53-2.71 (m, 3H), 3.95 (d, 1H, J = 7Hz), 4.03-4.08 (m, 1H), 4.16 (d, 1H, J = 8Hz), 4.18-4.23 (m, 1H ), 4.27-4. 34 (m, 2H), 4.87 (m, 1H), 4.94 (d, 1H, J = 8Hz), 5.09 (s, 1H),

 5.23 (d, 1H, J = 10Hz), 5.33 (dd, 1H, J = 1.5Hz, 17Hz), 5.64 (d, 1H, J = 7Hz),

5.92-6. 01 (m, 1H), 7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz) ) Step 2: 10-O-aryl-4,10-dideacetyl-7-0- (triimidazolylthiocarbonyl) -4-0-propionylbaccatin III

758 mg of the compound obtained in the above step 1 was dissolved in 75 ml of toluene, 500 mg of 1,1′-thiocarpodildimidazole and 154 mg of 4-dimethylaminopyridine were added, and the mixture was stirred at 80 ° C. for a while. Toluene was distilled off under reduced pressure, the residue was diluted with ethyl acetate, washed with water and saturated saline in that order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (elution solvent; black form: methanol = 50: 1 (v / v)) to obtain 790 mg of the title compound as a pale yellow solid. _{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 1.06 (s, 3H), 1.17 (s, 3H), 1.27 (t, 3H, J = 7Hz), 1.62 (s, 3H), 1.89-1.93 (m, 1H), 1.96 (s, 3H), 2.07 (s, 3H), 2, 28-2.35 (m, 2H), 2.59-2.74 (m, 2H),

 2.92-3.00 (m, 2H), 3.78-3.90 (m, 2H), 4.09 (d, 1H, J = 7Hz), 4.21 (d, 1H, J = 8Hz) ),

4.37 (d, 1H, J = 8Hz), 4.87 (br, lH), 4.96-5.02 (m, 4H), 5.58-5.69 (m, 2H),

6.16 (dd, 1H, J = 7Hz, 10Hz), 7.04 (s, 1H), 7.48 (t, 2H, J = 8Hz), 7.54 (s, 1H), 7.62 ( t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz), 8.30 (s, 1H)

Step 3: 10-0-aryl-7-dexoxy-4,10-dideacetyl-4-0-propionyl paccatin I I I

 780 mg of the compound obtained in the above step 2 was dissolved in 15 ml of toluene and 15 ml of 1,4-dioxane, and 20 mg of α, α'-azobisisobutyronitrile was added, followed by sufficient degassing and replacement with nitrogen. Then, 0.712 ml of triptyltin hydride was added, and the mixture was stirred at 90 ° C for 30 minutes. The reaction mixture was concentrated, and the resulting residue was purified by silica gel chromatography (eluent; solvent: methanol: methanol = 40: 1 (v / v)) to give 94 mg of the title compound as a colorless amorphous solid. Was.

_{'H-NMR (CDC1 3 /} TMS) <5 (ppm):

1.06 (s, 3H), 1.15 (s, 3H), 1.22 (t, 3H, J = 7Hz), 1.74 (s, 3H), 2.02 (s, 3H), 1.92-2.10 (m, 2H), 2.19-2.36 (m, 4H), 2.54-2.70 (m, 2H), 3.86 (d, 1H, J = 7Hz),

4.10-4.17 (m, 2H), 4.20 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz), 4.87 (m, 1H),

 4.92 (d, 1H, J = 8Hz), 5.07 (s, 1H), 5.22 (d, 1H, J = 10Hz),

 5.30 (dd, 1H, J = 1.5Hz, 17Hz), 5.62 (d, 1H, J = 7Hz), 5.92-6.02 (m, 1H),

7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz)

Step 4: 10-0-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilylloquine) -3-phenylpropionyl]- 7-deoxy-4,10-dideacetyl-4-0-propionylbaccatin III

 The compound obtained in the above Step 3 and (3R, 4S) -l- (tert-butoxycarbonyl) -4-phenyl-3- (triethylsilyloxy) azetidin-2-one were treated in the same manner as in Example 3. The reaction was carried out in the same manner as in 4 to give the title compound as a colorless amorphous solid.

 'H-NMRCCDC / TS) <5 (ppm):

 -0.30 (s, 3H), -0.13 (s, 3H), 0.76 (s, 9H), 1.19 (s, 3H), 1.23 (s, 3H),

1.31 (s, 9H), 1.38 (t, 3H, J = 7 Hz), 1.51-1.58 (m, 1H), 1.76 (s, 3H), 1.86 (s, 3H),

1.91-2.07 (m, 3H), 2, 16-2.28 (m, 1H), 2.37-2.46 (m, 1H), 2.74-2.96 (m, 2H),

 3.78 (d, 1H, J = 7Hz), 4.ll (d, 2H, J = 5Hz), 4.24 (d, 1H, J = 8Hz),

 4.34 (d, 1H, J = 8Hz), 4.48 (s, 1H), 4.92 (d, 1H, J = 8Hz), 5.03 (s, lH),

 5.22 (d, 1H, J = 10Hz), 5.26 (br, 1H), 5.31 (d, 1H, J = 17Hz), 5.46 (br, lH),

 5.69 (d, 1H, J = 7Hz), 5.91-6.00 (m, 1H), 6.25 (t, 1H, J = 8Hz), 7.28-7.41 (m, 5H),

7.49 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.14 (d, 2H, J = 8Hz)

Step 5: 13-O-[(2R, 3S) -3- (tert-butynecarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -7-deoxy_ 4, 10-dideacetyl-4- 0-propionyl -10- 0- (2-thiomoriholinoethyl) paccatin 111

 The compound obtained in Step 4 above was reacted in the same manner as in Step 1 of Example 2, and then reacted in the same manner as in Step 2 of Example 2 by using thiomorpholine instead of morpholine to convert the title compound to a non-colored amorphous Obtained as a solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 -0.30 (s, 3H), -0.13 (s, 3H), 0.76 (s, 9H), 1.16 (s, 3H), 1.22 (s, 3H),

1.31 (s, 9H), 1.38 (t, 3H, J = 7Hz), 1.53-1.57 (m, 1H), 1.75 (s, 3H), 1.89 (s, 3H), 1.95 (m, 2H), 2.04-2.12 (m, 1H), 2.21-2.28 (m, 1H), 2.39-2.45 (m, 1H),

 2.67-2.75 (m, 6H), 2.77-2.90 (m, 6H), 3.59-3.76 (m, 2H), 3.78 (d, 1H, J = 7Hz),

4.24 (d, 1H, J = 8Hz), 4.35 (d, 1H, J = 8Hz), 4.48 (s, lH), 4.91 (d, 1H, J = 8Hz),

5.01 (s, 1H), 5.28 (d, lH, J = 10Hz), 5.43 (br, lH), 5.68 (d, 1H, J = 7Hz),

6.25 (t, lH, J = 8Hz), 7.28-7.41 (m, 5H), 7.49 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.14 (d, 2H, J = 8Hz)

Step 6: 13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -7-deokin-4,10-dideacetyl-4 0-propionyl-10- 0- (2-thiomorpholinoethyl) paccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a colorless solid.

Melting point: 127-131 ° C

_{■ H-NMR (CDC1 3 /} TMS) δ (ppm):.

 1.16 (s, 3H), 1.21 (s, 3H), 1.21 (t, 3H, J = 7 Hz), 1.32 (s, 9H), 1.51-1.55 (m, 1H), 1.74 (s, 3H), 1.86 ( s, 3H), 1.90-2.09 (m, 2H), 2.19-2.29 (m, 2H),

 2.33-2.39 (m, 1H), 2.61-2.73 (m, 8H), 2.79-2.89 (m, 4H), 3.58-3.72 (m, 2H),

3.75 (d, 1H, J = 7Hz), 4.21 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz), 4.61 (s, 1H),

 4.88 (d, 1H, J = 8Hz), 5.01 (s, 1H), 5.24 (br, 1H), 5.31 (d, 1H, J = 10Hz),

 5.66 (d, 1H, J = 7Hz), 6.23 (t, 1H, J = 8Hz), 7.30-7.43 (m, 5H), 7.50 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.14 (d, 2H, J = 8Hz)

 IR (KBr): 3460, 3068, 2984, 2936, 2820, 1718, 1604, 1586 cm— '

MS-FAB: 935 (MH ⁺ )

Example 16

Step 1: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -4,10- Didacetyl -4- 0-propionyl-10-O- [2- (thiomorpholino-1-oxide) ethyl] -7-0-triethylsilylpaccatin III

 30 mg of the compound obtained in Step 1 of Example 6 was dissolved in 3 ml of methanol, and 0.271 ml of a 0.1 M aqueous solution of sodium metaperiodate was added thereto under ice-cooling, followed by stirring at 0 for 2 hours and at room temperature for 4 hours. The reaction solution was diluted with water and extracted with black-mouthed form. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was developed and purified by silica gel thin-layer chromatography (eluent; developing solvent: chloroform: methanol = 40: 1 (v / v)) to give 18.2 mg of the title compound as a colorless amorphous solid. Was.

'H-NMRCCDCh / T S) δ (ppm):

 0.52-0.63 (m, 6H), 0.96-1.01 (m, 30H), 1.19 (s, 3H), 1.20 (s, 3H), 1.35 (s, 9H), 1.37 (t, 3H, J = 7Hz), 1.67 (s, 3H), 1.87 (m, 1H), 1.93 (s, 3H), 2.32-2.36 (m, 2H),

2.45-2.52 (m, 1H), 2.75-2.89 (m, 10H), 3.19-3.25 (m, 2H), 3.60 (t, 2H, J = 6Hz),

3.82 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz), 4.42 (dd, 1H, J = 7H2, 10Hz), 4.89 (d, 1H, J = 8Hz), 4.94 (s, lH), 4.99 (s, 1H),

5.24 (d, 1H, J = 10Hz), 5.30 (d, 1H, J = 10Hz), 5.67 (d, 1H, J = 7Hz),

 6.18 (t, 1H, J = 8Hz), 6.27 (d, 1H, J = 3.5Hz), 6.37 (s, 1H), 7.40 (s, 1H),

7.47 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 8.11 (d, 2H, J = 8Hz)

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2_furyl) -2-hydroxypropionyl] -4,10-dideacetyl-4-0- Propionyl-10-O- [2- (thiomorpholino-1-oxide) ethyl] paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a colorless solid.

Melting point: 147-151. C

 'H-NMR (CDC / TMS) δ (ppm):

 1.19 (s, 3H), 1.21 (s, 3H), 1.30 (t, 3H, J = 7 Hz), 1.34 (s, 9H), 1.67 (s, 3H), 1.77-1.84 (m, 1H), 1.93 ( s, 3H), 2.28-2.37 (m, 2H), 2.46-2.54 (m, 1H),

2.69-2.76 (m, 2H), 2.78-2.92 (m, 8H), 3.20-3, 27 (m, 2H), 3.61-3.66 (m, 1H),

3.73-3.81 (m, 1H), 3.85 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz),

 4.26 (dd, 1H, J = 7Hz, 10Hz), 4.31 (d, 1H, J = 8H2), 4.70 (d, 1H, J = 2Hz),

 4.90 (d, 1H, J = 8Hz), 5.09 (s, 1H), 5.31 (d, 1H, J = 10Hz), 5.40 (d, 1H, J = 10Hz),

5.67 (d, 1H, J = 7Hz), 6.20 (t, 1H, J = 8Hz), 6.34 (d, 1H, J = 3Hz),

 6.38 (dd, 1H, J = 2Hz, 3Hz), 7.43 (s, 1H), 7.49 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz)

 IR (KBr): 3896, 3448, 2980, 2940, 1722, 1632, 1604, 1496 cm "'

MS-FAB: 957 (MH +)

Example π

Process 1: 10-0-aryl-10-deacetyl-13-0- (2,2,2-triclomouth ethoxyquincarbonyl) baccatin ΠΙ

563 mg of the compound obtained in Step 1 of Example 13 was dissolved in 50 ml of acetonitrile, 2.5 ml of pyridine and 7.5 ml of 48% hydrofluoric acid were added under ice-cooling, and the mixture was stirred at room temperature for 2 hours. After concentration, dilute with ethyl acetate, and add saturated aqueous sodium bicarbonate solution and 1N hydrochloric acid in this order. Washed. After drying over colorless sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was developed and purified by silica gel thin layer chromatography (developing solvent; chloroform: methanol = 40: 1 (v / v)) to obtain 415 mg of the title compound as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

1.15 (s, 3H), 1.22 (s, 3H), 1.68 (s, 3H), 1.76-1.82 (m, 1H), 1.98 (s, 3H),

2.38 (s, 3H), 2.35-2.42 (m, 2H), 2.54-2.62 (m, 1H), 3.93 (d, 1H, J = 7Hz),

4.04-4.08 (m, 2H), 4.13 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz),

 4.86 (s, 2H), 4.96 (d, 1H, J = 8Hz), 5.08 (s, 1H), 5.23 (d, 1H, J = 10.5Hz),

 5.32 (d, 1H, J = 17Hz), 5.66 (d, 1H, J = 7Hz), 5.91-6.00 (m, 2H),

7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz)

Step 2: 10-0-aryl-10-deacetyl-7-doxy-7-a-fluoro-13_0- (

2,2,2-triclomouth ethoxyquin carbonyl) paccatin III

 320 mg of the compound obtained in the above step 1 was dissolved in 30 ml of methylene chloride and cooled to -78 ° C. Then, 0.040 ml of getylaminosulfur trifluoride was added, and the mixture was stirred at -78 for 15 minutes and at room temperature for 30 minutes. The reaction solution was cooled again to -78 ° C, 0.080 ml of ethyl aminosulfur trifluorofluoride was added, and the mixture was stirred at -78 for 15 minutes and at room temperature for 60 minutes. After confirming the disappearance of the raw materials, the reaction solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was developed and purified by silica gel thin-layer chromatography (developing solvent; chloroform: acetone = 40: 1 (v / v)) to give 185 mg of the title compound as a colorless solid.

 'H-NMRCCDC / TMS) δ (ppm):

 1.14 (s, 3H), 1.20 (s, 3H), 1.71 (s, 3H), 1.90 (s, 3H), 2.12-2.62 (m, 4H),

2.39 (s, 3H), 4.07 (d, 1H, J = 7Hz), 4.11-4.14 (m, 2H), 4.23 (d, 1H, J = 8Hz),

 4.37 (d, 1H, J = 8Hz), 4.57 (dd, 1H, J = 5Hz, 47Hz), 4.85 (s, 2H),

5.02 (d, 1H, J = 9Hz), 5.12 (s, 1H), 5.22 (d, 1H, J = 10.5Hz), 5.31 (d, 1H, J = 17Hz),

5.74 (d, 1H, J = 7Hz), 5.90-6.00 (m, 2H), 7.49 (t, 2H, J = 8Hz),

7.62 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz)

Process 3: 10-O-aryl-10-deacetyl-7-dexoxy-7- -fluorobaccatin III 185.0 mg of the compound obtained in the above step 2 was dissolved in 20 ml of a mixed solvent of methanol: acetic acid = 1: 1 (v / v), 1 g of active zinc powder was added, and the mixture was stirred at 60 for 30 minutes. The insolubles were removed by filtration, the solvent was distilled off under reduced pressure, and the residue was azeotropically distilled with toluene. The obtained residue was diluted with ethyl acetate, washed with a saturated aqueous solution of sodium bicarbonate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was developed and purified by silica gel thin-layer chromatography (developing solvent; chloroform: acetone = 40: 1 (v / v)) to obtain 130 mg of the title compound as a colorless solid.

Contact point: 193-195. C

 ■ H-N RCCDC / TMS) 6 (ppm):

1.06 (s, 3H), 1.17 (s, 3H), 1..71 (s, 3H), 1.96 (s, 3H), 2.12 (m, 1H),

 2.25-2, 39 (m, 2H), 2.30 (s, 3H), 2.48-2.61 (m, 1H), 4.10- 4.13 (m, 3H).

4.27 (d, 1H, J = 8Hz), 4.35 (d, 1H, J = 8Hz), 4.55 (dd, 1H, J = 4.5Hz, 47.5Hz),

 4.86 (br, 1H), 5.02 (d, 1H, J = 8Hz), 5.ll (s, 1H), 5.27 (d, 1H, J = 10.5Hz),

 5.32 (d, 1H, J = 17Hz), 5.72 (d, 1H, J = 7Hz), 5.92-6.02 (m, 1H),

7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.13 (d, 2H. J = 8Hz)

IR (KBr): 3536, 3076, 2992, 2944, 2904, 1744, 1712, 1648, 1602 cm ' ¹ MS-FAB: 587 (MH +)

Step 4: 10-0-aryl- 13-0-[(2R, 3S) -3- (tert-butynecarbonylamino)-

2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-7-deoxy-7-a-fluoropaccatin III

 The compound obtained in the above step 3 and (3R, 4S) -1-tert-butoxycarbonyl-4-phenyl-3- (triethylsilyloxy) azetidin-2-one were treated in the same manner as in step 4 of Example 3. To give the title compound as a colorless amorphous solid.

 'H-NMRCCDCh / TMS) δ (ppm):

-0.30 (s, 3H), -0. Ll (s, 3H), 0.74 (s, 9H), 1.21 (s, 3H), 1.23 (s, 3H),

 1.31 (s, 9H), 1.75 (s, 3H), 1.83 (s, 3H), 2.17-2.60 (m, 4H), 2.56 (s, 3H),

4.05 (d, 1H, J = 7Hz), 4.12 (d, 1H ₍ J = 5.5Hz), 4.30 (d, 1H, J = 8Hz),

 4.38 (d, 1H, J = 8Hz), 4.53 (s, 1H), 4.59 (dd, 1H. J = 4Hz, 47Hz),

5.04 (d, 1H, J = 8Hz), 5.09 (d, 1H, .J = 2Hz), 5.21 (dd, 1H, J = 1.5Hz, 10.5Hz), 5.32 (dd, IH, J = 1.5Hz, 17Hz), 5.36 (d, IH, J = 10Hz), 5.45 (d, IH, J = 10Hz),

5.78 (d, IH, J = 7Hz), 5.91-6.00 (m, IH), 6.32 (t, IH, J = 8Hz), 7.28-7.40 (m, 5H), 7.50 (t, 2H, J = 8Hz) , 7.59 (t, IH, J = 8Hz), 8.15 (d, 2H, J = 8Hz)

Step 5: 13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-7- Deoxy-7-na-fluoro-10-O- (2-thiomorpholinoethyl) paccatin III

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 1 of Example 2, and then reacted in the same manner as in Step 2 of Example 2 using thiomorpholine instead of morpholine to give the title compound as a colorless amorphous solid. As obtained.

'H-NMRCCDC / TMS) δ (ppm):

 -0.32 (s, 3H), -0. Ll (s, 3H), 0.74 (s, 9H), 1.18 (s, 3H), 1.22 (s, 3H),

1.31 (s, 9H), 1.74 (s, 3H), 1.85 (s, 3H), 2.12-2.59 (m, 4H), 2.56 (s, 3H),

 2.67-2.72 (m, 6H), 2.82-2.85 (m, 4H), 3.62-3.70 (m, 2H), 4.04 (d, IH, J = 7Hz),

4.30 (d, 1H, J = 8Hz), 4.37 (d, IH, J = 8Hz), 4.52 (s, 1H), 4.59 (dd, IH, J = 4Hz, 47Hz), 5.03 (d, IH, J = 8Hz), 5.08 (s, 1H), 5.35 (d, IH, J = 10Hz), 5.48 (d, 1H, J = 10Hz),

 5.77 (d, IH, J = 7Hz), 6.31 (t, IH, J = 8Hz), 7.28-7.40 (m, 5H),

7.50 (t, 2H, J = 8H2), 7.60 (t, IH, J = 8Hz), 8.14 (d, 2H, J = 8Hz)

Step 6: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy

-3-Phenylpropionyl] -10-deacetyl-7-deoxy-7-a-fluoro-10-0- (2-thiomorpholinoethyl) paccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a colorless solid.

Melting point: 142-146. C

 'H-NMR (CDCh / TMS) <5 (ppm):

1.17 (s, 3H), 1.20 (s, 3H), 1.34 (s, 9H), 1.72 (s, 3H), 1.80 (s, 3H),

 2.15-2.60 (m, 4H), 2.38 (s, 3H), 2.66-2.72 (m, 6H), 2.79-2.84 (m, 4H),

 3.59-3.72 (m, 2H), 4.02 (d, IH, J = 7Hz), 4.27 (d, IH, J = 8Hz), 4.35 (d, IH, J = 8Hz), 4.62 (s, lH), 4.56 (dd, IH, J = 4Hz, 47Hz), 5.00 (d, 1H, J = 8Hz), 5.07 (s, IH),

5.30 (d, IH, J = 10Hz), 5.40 (d, IH, J = 10Hz), 5.75 (d, IH, J = 7Hz), 6.23 (t, IH, J = 8Hz), 7.32-7.39 (m, 5H), 7.50 (t, 2H, J = 8H2), 7.61 (t, IH, J = 8H2 ), 8.13 (d, 2H, J = 8Hz)

 IR (KBr): 3452, 3068, 2940, 2816, 1742, 1714, 1604, 1586 cm "'

 MS-FAB: 939 (MH ^)

 Example 18

Step 1: 10-0-aryl-4,10-dideacetyl-4-0-propionyl-13-0- (2,2,2-trichloroethoxycarbonyl) -7-0-triethylsilylpaccatin III The compound obtained in Step 3 of Example 3 was reacted in the same manner as in Step 1 of Example 13 to give the title compound as a colorless amorphous solid.

'H-NMR (CDCla / TMS) δ (pm):

 0.50-0.64 (m, 6H), 0.95 (t, 9H, J = 8Hz), 1.16 (s, 3H), 1.23 (s, 3H),

1.33 (t, 3H, J = 7Hz), 1.67 (s, 3H), 1.85- 1.91 (m, 1H), 1.99 (s, 3H),

2.30-2.41 (m, 2H), 2.46-2.54 (m, 1H), 2.64-2.76 (m, 2H), 3.87 (d, 1H, J = 7Hz), 4.10-4.14 (m, 2H), 4.13 (d , 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz),

4.45 (dd, 1H, J = 7Hz, 10Hz), 4.84 and 4.88 (each d, each 1H, J = 12Hz),

 4.89 (d, 1H, J = 8Hz), 5.02 (s, 1H), 5.21 (dd, 1H, J = l.5Hz, 10Hz),

 5.30 (dd, 1H, J = 1.5Hz, 17Hz), 5.64 (d, 1H, J = 7Hz), 5.94-6.02 (m, 1H),

 6.05 (t, 1H, J = 8Hz), 7.47 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz) Step 2: 4,10- Didacetyl -4- 0-propionyl -10-O- (2-thiomorpholinoethyl) -13- 0- (2,2,2-trichloromouth ethoxycarbonyl) -7-0- triethylsilyl paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 2 of Example 13 to give the title compound as a colorless amorphous solid.

'H-NMRCCDC / TMS) δ (ppm):

0.52-0.64 (m, 6H), 0.96 (t, 9H, J = 8Hz), 1.14 (s, 3H), 1.20 (s, 3H),

1.33 (t, 3H, J = 7Hz), 1.67 (s, 3H), 1.85-1.91 (m, 1H), 2.00 (s, 3H),

 2.33-2.40 (m, 2H), 2.46-2.53 (m, 1H), 2.67-2.76 (m, 8H), 2.83 (m, 4H),

 3.48-3.66 (m, 2H), 3.85 (d, 1H, J = 7Hz), 4.13 (d, 1H, J = 8Hz), 4.15 (s, 1H),

 4.32 (d, 1H, J = 8Hz), 4.45 (dd, 1H, J = 7Hz, 10Hz),

4.83 and 4.88 (each d, each 1H, J = 12Hz), 4.87 (d, 1H, J = 8Hz), 4.96 (s, 1H),

 5.63 (d, 1H, J = 7Hz), 6.04 (t, 1H, J = 8Hz), 7.47 (t, 2H, J = 8Hz),

 7.61 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz)

Step 3: 4, 10-dideacetyl-4-0-propionyl-10-0- (2_thiomorpholinoethyl) -7-0-tritylsilylpaccatin III The compound obtained in the above Step 2 was reacted in the same manner as in Step 3 of Example 13 to give the title compound as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 0.50-0.65 (m, 6H), 0.96 (t, 9H, J = 8Hz), 1.05 (s, 3H), 1.17 (s, 3H),

1.24 (t, 3H, J = 7Hz), 1.66 (s, 3H), 1.85-1.91 (m, 1H), 2.07 (s, 3H),

 2.24 (d, 2H, J = 9Hz), 2.46-2.55 (m, 2H), 2.57-2.64 On, 2H), 2.66-2.74 (m, 6H), 2.84-2.89 (m, 4H), 3.55-3.67 ( m, 2H), 3.87 (d, 1H, J = 7Hz), 4.14 (d, 1H, J = 8Hz), 4.29 (d, 1H, J = 8Hz), 4.44 (dd, 1H, J = 7Hz, 10Hz) , 4.86 (br, lH),

4.91 (d, 1H, J = 8Hz), 4.98 (s, 1H), 5.60 (d, 1H, J = 7Hz), 7.46 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz) , 8. ll (d, 2H, J = 8Hz)

Step 4: 13-0-[(2,3-threo) -3- (tert-butoxycarbonylamino) -5-methyl-2- (triethylsilyloxy) -4-hexenyl] -4,10 -Didecyl-4-O-propionyl-10-O- (2-thiomorpholinoethyl) _7-0- Triethylsilyl paccatin III

 The compound obtained in the above step 3 and (3,4-cis) -tri-tert-butynecarbonyl-4-isobutenyl-3- (triethylsilyloxy) azetidin-2-one were treated in the same manner as in step 4 of Example 3. Reaction yielded the title compound as a colorless amorphous solid.

'H-NMRCCDCh / TMS) δ (ppm):

 0.53-0.70 (m, 12H), 0.93-1.03 (m, 18H), 1.19 (s, 6H), 1.26-1.32 (m, 3H),

1.35 and 1.39 (each s, total 9H), 1.67 (s, 3H), 1.77 (s, 3H), 1.81 (s, 3H),

1.86 and 1.89 (each s, total 3H), 2.12 (m, 2H), 2.34-2.47 (m, 3H),

2.65-2.70 (m, 6H), 2.83 (m, 4H), 3.56-3.60 (m, 2H),

3.80 and 3.84 (each d, total 1H, J = 7Hz), 4.18-4.31 (m, 3H), 4.41 (m, 1H),

 4.75 and 5.02 (each br, total 1H), 4.85 (m, 2H),

4.92 and 4.97 (each s, total 1H), 5.26 and 5.31 (each d, total 1H, J = 10Hz),

5.64-5.66 (m, 1H), 6.1 Km, 1H), 7.42-7.60 (m, 3H),

8.06 and 8.11 (each d, total 2H, J = 8Hz)

Step 5: 13-O-[(2S, 3R) -3- (tert-butoxycarbonylamino) -2-hidequin-5-methyl-4-hexenyl] -4,10-dideacetyl-4 0-propionyl -10-O -(2-thiomorpholinoethyl) pacchinin 111 and 13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-5-methyl-4-hexenyl] -4 , 10-Dideacetyl-4-0-propionyl-10-O- (2-thiomorpholinoethyl) paccatin III

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 7 of Example 3 to give each of the title compounds as a colorless solid.

(2S, 3R) body

Melting point: 142-145 ° C

■ H-NMRCCDCh / TMS) δ (ppm):

1, 18 (s, 6H), L28 (t, 3H, J = 7Hz), 1.39 (s, 9H), 1.68 (s, 3H), 1.79 (s, 3H),

1.82 (s, 3H), 2.00 (m, 1H), 2.11-2.16 (m, 2H), 2.15 (s, 3H), 2.38-2.62 (m, 3H),

2.67-2.73 (m, 6H), 2.79-2.87 (m, 4H), 3.63-3.65 (m, 1H), 3.76-3.79 (m, 1H),

3.89 (d, 1H, J = 7Hz), 4.08 (s, lH), 4.16 (d, 1H, J = 8Hz), 4.29 (d, 1H, J = 8Hz),

4.30 (dd, 1H, J = 7Hz, 10Hz), 4.78 (s, 1H), 4.76-4.80 (m, 1H), 4.90 (d, 1H, J = 8Hz), 5.07 (s, 1H), 5.29 (d , 1H, J = 7Hz), 5.66 (d, 1H, J = 7Hz), 6.01 (t, 1H, J = 8Hz),

7.46 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.05 (d, 2H, J = 8Hz)

IR (KBr): 3460, 2980, 2940, 2824, 2352, 1722, 1604, 1586 cm

MS-FAB: 929 (ΜΗ)

(2R.3S) body

Melting point: 146-149 ° C

 (Ή-NMRCCDCh / TMS) δ (ppm):

 1.19 (s, 3H), 1.20 (s, 3H), 1.27 (t, 3H, J = 7 Hz), 1.35 (s, 9H), 1.67 (s, 3H), 1.78 (s, 6H), 1.84 (m, 1H), 1.93 (s, 3H), 2.35- 2.37 (m, 2H), 2.53-2.71 (m, 9H), 2.79-2.89 (m, 4H), 3.63- 3.66 (m, 1H), 3.72-3.76 ( m, 1H), 3.86 (d, 1H, J = 7Hz), 4.16 (s, 1H), 4.17 (d, 1H, J = 8Hz), 4.27 (dd, 1H, J = 7Hz, 10Hz),

 4.31 (d, 1H, J = 8Hz), 4.70-4.79 (m, 2H), 4.91 (d, 1H, J = 8Hz), 5.06 (s, 1H),

 5.36 (d, 1H, J = 7Hz), 5.67 (d, 1H, J = 7Hz), 6.14 (t, 1H, J = 8Hz),

7.46 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz)

IR (KBr): 3464, 3068, 2980, 2940, 2820, 1716, 1604, 1584 cm "' MS-FAB: 929 (ΜΤ)

 Example 19

Step 1: 10-0-aryl-13-0- [3-61 "butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionyl] -4,10-dideacetyl-4 -0- propionyl -7- 0- triethylsilylpaccatin III (isomer Α, isomer Β)

Dissolve 245 mg of 3- (tert-butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionic acid and 182 m of 2,2′-dibiridylcarbonate in 6 ml of toluene and add 1 ml at room temperature. Stirred for 0 minutes. Then, 100 mg of the compound obtained in Step 3 of Example 3 and 17 mg of 4-dimethylaminoviridine were added, and the mixture was heated and stirred at 70 at 70 ° C. After cooling, the reaction solution was diluted with ethyl acetate, washed with 1N hydrochloric acid, a saturated aqueous solution of sodium bicarbonate and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel thin eye chromatography (developing solvent; ethyl ether: hexane = 1: 1 ( v / v)) to obtain two isomers A (low polarity compound) (56.3 m) and isomer B (high polarity compound) 51.0 mg, respectively.

Isomer A

 ■ H-NMRCCDC / TMS) δ (ppm):

0.51-0.64 (m, 6H), 0.95 (t, 9H, J = 8Hz), 1.21 (s, 3H), 1.24 (s, 3H),

 1.31 (t, 3H, J = 7Hz), 1.42 (s, 9H), 1.68 (s, 3H), 1.87 (s, 3H), 1.85-1.92 (m, 1H),

2.25-2.27 (m, 2H), 2.45-2.53 (m, 1H), 2.59-2.61 (m, 2H), 3.79 (d, 1H, J = 7Hz),

3.99-4.07 (m, 2H), 4.15 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz),

4.41 (dd, 1H, J = 7Hz, 10Hz), 4.87 (d, 1H, J = 8Hz), 4.96 (s, 1H),

5.19 (d, 1H, J = 9Hz), 5.29 (dd, 1H, J = 1.5Hz, 17Hz), 5.38 (d, 1H, J = 10Hz),

 5.62 (m, 1H), 5.66 (d, 1H, J = 7Hz), 5.92-6.02 (m, 1H), 6.27 (t, 1H. J = 8Hz),

 6.40-6.44 (m, 2H), 7.45-7.50 (m, 3H), 7.61 (t, 1H, J = 8Hz), 8.11 (d, 2H, J = 8Hz) Isomer B

 ■ H-NMRCCDCh / TMS) 6 (ppm):

0.51-0.64 (m, 6H), 0.95 (t, 9H, J = 8Hz), 1.21 (s, 3H), 1.24 (s, 3H),

 1.29 (t, 3H, J = 7Hz), 1.45 (s, 9H), 1.68 (s, 3H), 1.90 (s, 3H), 1.87-1.93 (m, 1H), 2.26 (d, 2H, J = 9Hz ), 2.45-2.60 (m, 3H), 3.79 (d, 1H, J = 7Hz), 3.99-4.09 (m, 2H), 4.14 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.41 (dd, 1H, J = 7Hz, 10Hz),

 4.87 (d, 1H, J = 8Hz), 4.97 (s, 1H), 5.19 (dd, 1H, J = 1.5Hz, 10.5Hz),

5.29 (dd, 1H, J = 1.5Hz, 17Hz), 5.38 (d, 1H, J = 10Hz), 5.60 (m, 1H),

 5.66 (d, 1H, J = 7Hz), 5.93-6.03 (m, 1H), 6.23 (t, 1H, J = 8Hz), 6.39-6.45 (m, 2H),

7.43 (d, 1H, J = 1.5Hz), 7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz).

 8.09 (d, 2H, J = 8Hz)

Step 2: 13-0- [3- (tert-butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionyl] -4,10-dideacetyl-4-O-propionyl-10- O- (2-thiomorpholinoethyl) -7-0- Triethylsilylpaccatin 111 (isomer A, isomer B)

The compounds obtained in the above Step 1 were reacted in the same manner as in Step 1 of Example 2, and then reacted in the same manner as in Step 2 of Example 2 using thiomorpholine instead of morpholine. To give the title compounds (isomer A and isomer B) as amorphous solids respectively.

 ■ H-NMRCCDC / TMS) δ (ppm):

0.49- 0.64 (m, 6H), 0.96 (t, 9H, J = 8Hz), 1.20 (s, 6H), 1.30 (t, 3H, J = 7Hz),

 1.42 (s, 9H), 1.67 (s, 3H), 1.87 (s, 3H), 1.89-1.93 (m, 1H), 2.24-2.30 (m, 2H),

2.44-2.52 (m, 1H), 2.59-2.61 (m, 2H), 2.66-2.73 (m, 8H), 2.83-2.95 (m, 4H),

3.48-3.65 (m, 2H), 3.78 (d, 1H, J = 7Hz), 4.15 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz),

4.42 (dd, 1H, J = 7Hz, 10Hz), 4.87 (d, 1H, J = 8Hz), 4.91 (s, lH),

5.36 (d, 1H, J = 10Hz), 5.55-5.63 (m, 1H), 5.65 (d, 1H, J = 7Hz),

 6.25 (t, 1H, J = 8Hz), 6.40-6.43 (m, 2H), 7.45-7.49 (m, 3H), 7.61 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz)

Isomer B

 'H-NMRCCDCh / TMS) δ (ppm):

0.49-0.64 (m, 6H), 0.96 (t, 9H, J = 8Hz), 1.19 (s, 3H), 1.20 (s, 3H),

 1.29 (t, 3H, J = 7Hz), 1.45 (s, 9H), 1.67 (s, 3H), 1.90 (s, 3H), 1.87-1.91 (m, 1H), 2.25 (d, 2H, J = 9Hz ), 2.44-2.61 (m, 3H), 2.66-2.73 (m, 8H), 2.83-2.85 (m, 4H), 3.48-3.65 (m, 2H), 3.78 (d, 1H, J = 7Hz), 4.14 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.43 (dd, 1H, J = 7Hz, 10Hz), 4.87 (d, 1H, J = 8Hz), 4.92 (s, 1H ),

5.37 (d, 1H, J = 10Hz), 5.58-5.61 (ra, 1H), 5.65 (d, 1H, J = 7Hz),

 6.21 (t, 1H, J = 8Hz), 6.39-6.44 (m, 2H), 7.43-7.50 (m, 3H), 7.61 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz)

Step 3: 13-0- [3- (tert-butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionyl] -4,10-dideacetyl-4-0-propionyl- 10-O- (2-thiomorpholinoethyl) paccatin III (isomer A, isomer B)

 The compounds obtained in Step 2 above were reacted in the same manner as in Step 7 of Example 3 to give the title compounds (isomer A and isomer B) as colorless solids.

Isomer A

Melting point: 136-139 ° C 'HN RCCDCh / TMS) <5 (ppm):

 1.19 (s, 3H), 1.21 (s, 3H), 1.29 (t, 3H, J = 7 Hz), 1.41 (s, 9H), 1.67 (s, 3H), 1.87 (s, 3H), 1.81-1.84 ( m, 1H), 2.21-2.32 (m, 2H), 2.54-2.62 (m, 3H), 2.66-2.71 (m, 8H), 2.78-2.90 (m, 4H), 3.60-3.65 (m, IH), 3.71-3.79 (m, IH), 3.84 (d, IH, J = 7Hz), 4.13 (d, IH, J = 8Hz), 4.28 (dd, 1H, J = 7Hz, 10Hz),

 4.31 (d, IH, J = 8Hz), 4.89 (d, IH, J = 8Hz), 5.02 (s, 1H), 5.36 (d, IH, J = 10Hz), 5.57-5.63 (m, IH), 5.67 (d, IH, J = 7Hz), 6.25 (t, IH, J = 8Hz), 6.40-6.43 (m, 2H), 7.45-7.50 (m, 3H), 7.61 (t, IH, J = 8Hz), 8.10 (d, 2H, J = 8Hz)

IR (Br): 3464, 2984, 2944, 2816, 1768, 1724, 1604, 1500 cm— ¹

MS-FAB: 961 (MH +)

Isomer B

Melting point: 138-142. C

■ H-NMRCCDCh / TMS) δ (ppm):

 1.19 (s, 3H), 1.20 (s, 3H), 1.27 (t, 3H, J = 7 Hz), 1.45 (s, 9H), 1.67 (s, 3H), 1.90 (s, 3H), 1.77-1.84 ( m, IH), 2.25 (d, 2H, J = 9Hz), 2.50-2.61 (m, 3H),

2.66-2.72 (m, 8H), 2.77-2.89 (m, 4H), 3.60-3.65 (m, IH), 3.74-3.79 (m, IH),

3.82 (d, IH, J = 7Hz), 4.15 (d, IH, J = 8Hz), 4.31 (d, IH, J = 8Hz),

 4.27 (dd, 1H, J = 7Hz, 10Hz), 4.89 (d, 1H, J = 8Hz), 5.03 (s, IH),

 5.37 (d, IH, J = 10Hz), 5.55-5.61 (m, IH), 5.67 (d, IH, J = 7Hz),

6.19 (t, IH, J = 8Hz), 6.39-6.43 (m, 2H), 7.43 (d, IH, J = 1.5Hz),

 7.48 (t, 2H, J = 8Hz), 7.62 (t, IH, J = 8Hz), 8.09 (d, 2H, J = 8Hz)

IR (KBr): 3464, 2980, 2944, 2820, 1766, 1722, 1604, 1500 cm— ¹

MS-FAB: 961 (MH ⁺ )

Example 20

Step 1: 10-Deacetyl -10-O- (2-pyridylmethyl) -7-0- Triethylsilylbaccatin II 1

7-0- Triethylunrilpaccatin 111 100 mg was dissolved in tetrahydrofuran 4 ml, and -78. Cooled to C. Next, 0.378 ml of n-butyllithium (1.61 M hexane solution) was added dropwise. After 15 minutes, a solution of 57.7 mg of 2-pyridylmethylbumidamide bromide in 1 ml of dimethyl sulfoxide was added dropwise, and the mixture was heated to 0 ° C and stirred for 1 hour. A saturated aqueous solution of sodium bicarbonate was added, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue is subjected to silica gel thin layer chromatography. (Developing solvent; black form: methanol = 20: 1 (v / v)) to give 25.1 mg of the title compound as a colorless amorphous solid.

 ■ H-NMRCCDC / TMS) δ (ppm):

 0.47-0.61 (m, 6H), 0.92 (t, 9H, J = 8Hz), 1.06 (s, 3H), 1.24 (s, 3H), 1.70 (s, 3H), 1.86-1.93 (m, 1H), 2.09 (s, 3H), 2.21-2.33 (m, 2H), 2.28 (s, 3H),

 2.46-2.54 (m, 1H), 3.91 (d, 1H, J = 7Hz), 4.16 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz), 4.45 (dd, 1H, J = 7Hz, 10Hz), 4.7KAB evening d, each 1H, J = 13Hz), 4.88 (br, 1H), 4.96 (d, 1H, J = 8Hz), 5.22 (s, 1H), 5.64 (d, 1H, J = 7Hz), 7.18-7.21 (m, 1H),

7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 7.72-7.76 (m, 2H), 8.10-8.12 (m, 2H), 8.50 (d, 1H, J = 5Hz)

Step 2: 13-0-[(2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, 0- (4-methoxybenzylidene) -3-phenylisoselinyl]- 10-Decetyl -10-O- (2-pyridylmethyl) -7-0-Triethylsilylpaccatin III

 Dissolve 80.0 mg of (4S, 5R) -3-tert-butoxycarbonyl-2- (4-methoxyphenyl) -oxazolidin-5-carboxylic acid in 2 ml of ethyl ethate, add 49.5 mg of dicyclohexylcarbodiimide, and add room temperature. And stirred for 15 minutes. Next, 50.0 mg of the compound obtained in the above step 1 and 2-dimethylaminopyridine were added, and the mixture was stirred for 1 hour. After filtering off insolubles, the mother liquor was washed with a saturated aqueous solution of sodium bicarbonate and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was developed and purified by silica gel thin-layer chromatography (developing solvent; chloroform: methanol = 40: 1 (v / v)) to obtain 65.1 mg of the title compound as a colorless amorphous solid. .

lH-NMR (CDCl ₃ / TMS) δ (ppm):

 0.45-0.55 (m, 6H), 0.89 (t, 9H, J = 8Hz), 1.05 (s, 9H), 1.19 (s, 3H), 1.25 (s, 3H), 1.58 (br, 3H), 1.65 ( s, 3H), 1.84 (br, 3H), 1.87-1.91 (m, 1H),

2.05-2.17 (m, 2H), 2.41-2.45 (m, 1H), 3.72 (d, 1H, J = 7Hz), 3.77 (s, 3H),

4.09 (d, 1H, J = 8Hz), 4.22 (d, 1H, J = 8Hz), 4.33 (dd, 1H, J = 7Hz, 10Hz),

 4.56 (d, 1H, J = 5Hz), 4.65 (AB type d, each 1H, J = 14Hz), 4.84 (d, 1H, J = 8Hz),

 5.08 (s, 1H), 5.40 (br, 1H), 5.63 (d, 1H, J = 7Hz), 6.15 (br, 1H), 6.40 (br, 1H),

6.93 (d, 2H, J = 9Hz), 7.17-7.21 (m, 1H), 7.41-7.50 (m, 9H), 7.60-7.64 (m, 2H), 7.69-7.73 (m, 1H), 8.03 (d, 2H, J = 8Hz), 8.51 (d, 1H, J = 4.5Hz)

Step 3: 13-0-[(2R, 3S) -N- (tert-butynecarbonyl) -2,3-N, 0- (4-methoxybenzylidene) -3-phenylisoselinyl] -10- deacetyl-10- 0- (2-pyridylmethyl)

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a colorless amorphous solid.

lH-NMR (CDCl ₃ / TMS) δ (ppm):

 0.81 (br, 3H), 1.03 (s, 9H), 1.18 (s, 3H), 1.20 (s, 3H), 1.66 (s, 3H),

1.74 (br, 3H), 1.86-1.94 (m, 1H), 1.97-2.15 (m, 2H), 2.45-2.52 (m, 1H),

3.59 (d, 1H, J = 7Hz), 3.82 (s, 3H), 4.10 (d, 1H, J = 8Hz),

 4.16 (dd, 1H, J = 7Hz, lOHz), 4.21 (d, 1H, J = 8Hz), 4.50 (s, lH),

 4.75 (d, 1H, J = 13Hz), 4.87 (d, 1H, J = 13Hz), 4.88 (d, 1H, J = 8Hz), 5.03 (s, 1H),

5.35 (br, 1H), 5.60 (d, 1H, J = 7Hz), 6.04 (br, 1H), 6.35 (br, 1H),

 6.86 (d, 2H, J = 8Hz), 7.29-7.39 (m, 8H), 7.47 (t, 2H, J = 8Hz), 7.54-7.61 (m, 2H), 7.82 (t, 1H, J = 8Hz) , 8.01 (d, 2H, J = 8Hz), 8.48 (d, 1H, J = 4.5Hz)

Step 4: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-fuunylpropionyl] -10-deacetyl -10-0- (2-pyridylmethyl ) Packa Chin III

 34.1 mg of the compound obtained in the above step 3 was dissolved in 4 ml of methanol, and 16.2 mg of tosylic acid was added at room temperature, followed by stirring for 2 hours. After dilution with a saturated aqueous solution of sodium bicarbonate, extraction with ethyl acetate and drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The resulting residue was developed and purified by silica gel thin broth chromatography (developing solvent; black form: methanol = 20: 1 (v / v)), and then lyophilized from 1,4-dioxane to give 28.3 mg of the title compound. Obtained as a white solid.

Melting point: 152-157 ° C

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 1.15 (s, 3H), 1.20 (s, 3H), 1.25 (s, 3H), 1.32 (s, 9H), 1.73 (s, 3H),

1.92-1.99 (m, 1H), 2.21 (d, 2H, J = 8Hz), 2.32 (s, 3H), 2.50-2.58 (m, 1H),

3.71 (d, 1H, J = 7Hz), 4.19 (d, 1H, J = 8Hz), 4.25 (dd, 1H, J = 7Hz, 10Hz), 4.29 (d, 1H, J = 8Hz), 4.52 (s, IH), 4.89 (d, IH, J = 12Hz), 4.92 (d, 1H, J = 12Hz),

4.95 (d, IH, J = 8Hz), 5.18 (s, 1H), 5.21 (d, IH, J = 10Hz), 5.36 (d, IH, J = 10Hz),

5.66 (d, lH, J = 7Hz), 6.12 (t, IH, J = 8Hz), 7.29-7.39 (m, 6H), 7.48 (t, 2H, J = 8Hz ),

7.59 (d, 2H, J = 7Hz), 7.81 (t, IH, J = 8Hz), 8.09 (d, 2H, J = 8Hz), 8.51 (d, 1H, J = 5Hz) ) IR (KBr): 3452, 3068, 2980, 2940, 2504, 1722, 1600 cm— ¹

 MS-FAB: 899 (MH10)

 Example 21

Step 1: 10-Deacetyl -10-0- (3-pyridylmethyl) -7-0-Triethylsilylbaccatin 1 1 1 The title compound was obtained as a colorless amorphous solid by reacting in the same manner as in Step 1 of Example 20 using 3-pyridylmethylbumidamide bromide instead of 2-pyridylmethylbumidamide bromide. .

 ■ H-N RCCDCh / TMS) δ (ppm):

0.49-0.63 (m, 6H), 0.95 (t, 9H, J = 8Hz), 1.07 (s, 3H), 1.21 (s, 3H), 1.69 (s, 3H), 1.82-1.93 (m, 1H), 2.07 (s, 3H), 2.25-2.31 (m, 2H), 2.29 (s, 3H),

2.44-2.55 (m, 1H), 3.89 (d, 1H, J = 7Hz), 4.16 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz), 4.46 (dd, 1H, J = 7Hz, 10Hz), 4.55 (d, 1H, J = 12Hz), 4.68 (d, 1H, J = 12Hz),

4.91 (t, lH, J = 8Hz), 4.97 (d, 1H, J = 8Hz), 5.13 (s, 1H), 5.63 (d, 1H, J = 7Hz), 7.29-7.33 (m, 1H), 7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 7.83 (d, 1H, J = 8Hz), 8.11 (d, 2H, J = 8Hz), 8.53-8.59 (m, 2H )

Step 2: 13-0-[(2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, 0- (4-methoxybenzylidene) -3-phenylisoselinyl] -10- Decetyl-10-O- (3-pyridylmethyl) -7-0- Triethylsilylpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 2 of Example 20 to obtain the title compound as a colorless amorphous solid.

■ H-MRCCDC AMS) <5 (ppm):

 0.45-0.59 (m, 6H), 0.93 (t, 9H, J = 8 Hz), 1.06 (s, 9H), 1.19 (s, 3H), 1.21 (s, 3H), 1.56 (br, 3H), 1.64 ( s, 3H), l, 85 (br, 3H), 1.86-1.92 (m, 1H),

2.04-2.24 (m, 2H), 2.39-2.47 (m, 1H), 3.70 (d, 1H, J = 7Hz), 3.77 (s, 3H),

4.08 (d, 1H, J = 8Hz), 4.22 (d, 1H, J = 8Hz), 4.35 (dd, 1H, J = 7Hz, 10Hz),

4.48 (d, 1H, J = llHz), 4.56 (d, 1H, J = llHz), 4.57 (s, 1H), 4.84 (d, 1H, J = 8Hz), 4.98 (s, 1H), 5.42 (br , LH), 5.61 (d, 1H, J = 7 Hz), 6.12 (br, 1H), 6.39 (br, 1H), 6.93 (d, 2H, J = 9 Hz), 7.29-7.32 (m, 1H), 7.38 -7.50 (m, 9H), 7.62 (t, 1H, J = 8Hz), 7.78 (d, 1H, J = 8Hz), 8.02 (d, 2H, J = 8Hz), 8.54-8.59 (m, 2H)

Step 3: 13-0-[(2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, O- (4-methoxybenzylidene) -3-phenylisoselinyl]- 10-Deacetyl -10-O- (3-pyridylmethyl) paccatin ΠΙ

The compound obtained in the above Step 2 was reacted in the same manner as in Step 3 of Example 20 to give the title compound. Obtained as a colorless amorphous solid.

 lH-NMR (CDCh / TMS) δ (ppm):

 1.05 (s, 9H), 1.19 (s, 3H), 1.21 (s, 3H), 1.34 (s, 3H), 1.65 (s, 3H),

1.73 (br, 4H), 2.03-2.22 (m, 2H), 2.46-2.53 (m, 1H), 3.71 (d, 1H, J = 7Hz),

3.80 (s, 3H), 4.09 (d, 1H, J = 8Hz). 4.15 (dd, 1H, J = 7Hz, 10Hz).

 4.21 (d, 1H, J = 8Hz), 4.55 (s, 1H), 4.56 (d, 1H, J = 13Hz), 4.73 (d, 1H, J = 13Hz), 4.85 (d, 1H, J = 8H2) , 4.93 (s, 1H), 5.39 (br, 1H), 5.62 (d, 1H, J = 7Hz),

 6.09 (br, 1H), 6.36 (br, 1H), 6.93 (d, 2H, J = 8Hz), 7.30 (dd, 2H, J = 5Hz, 8Hz),

 7.37-7.44 (m, 6H), 7.48 (t, 2H, J = 8Hz), 7.62 (t, 1H, J = 8Hz), 7.77 (d, 1H, J = 8Hz), 8.00-8.03 (m, 2H) , 8.52 (dd, 1H, J = 1.5Hz, 5Hz), 8.57 (d, 1H, J = 1.5Hz)

Step 4: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3--3-phenylpropionyl] -10-deacetyl- 10-0- (3-pyridylmethyl)力

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 4 of Example 20 to give the title compound as a colorless solid.

Contact point: 158-163. C

'H-NMRCCDCh / TMS) δ (ppm):

 1.22 (s, 3H). 1.25 (s, 3H), 1.34 (s, 9H), 1.61 (s, 3H), 1.71 (s.3H),

1.81-1.87 (m, 1H), 2.26 (m, 2H), 2.34 (s, 3H), 2.51-2.55 (m, 1H),

3.81 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz), 4.21 (dd, 1H, J = 7Hz, 10Hz),

 4.30 (d, 1H, J = 8Hz), 4.59 (d, 1H, J = 12Hz), 4.60 (s, 1H), 4.77 (d, 1H, J = 12Hz),

4.93 (d, 1H, J = 8Hz), 5.03 (s, lH), 5.25 (d, 1H, J = 10Hz), 5.45 (d, 1H, J = 10Hz),

5.68 (d, 1H, J = 7Hz), 6.20 (t, 1H, J = 8Hz), 7.28-7.39 (m, 6H), 7.49 (t, 2H, J = 8Hz), 7.61 (d, 2H, J = 8Hz), 7.81 (d, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz), 8.48-8.49 (m, 1H), 8.55 (s, 1H)

 IR (KBr): 3448, 3068, 2980, 2940, 2356, 1720, 1602 cm "

MS-FAB: 899 (MT) Example 22

Step 1: 10-Deacetyl -10-O- (4-pyridylmethyl) -7-0- Triethylsilylbaccatin III

 The title compound was obtained as a colorless amorphous solid by reacting in the same manner as in Step 1 of Example 20 using 4-pyridylmethylbumidamide bromide instead of 2-pyridylmethylbumidamide bromide.

_{'HN R (CDC1 3 / TS} ) δ (ppm):

0.51-0.63 (m, 6H), 0.94 (t, 9H, J = 8Hz), 1.09 (s, 3H), 1.24 (s, 3H), 1.69 (s, 3H), 1.87-1.93 (m, 1H), 2.06 (s, 3H), 2.27-2.31 (m, 2H), 2.28 (s, 3H),

 2.47-2.55 (m, 1H), 3.89 (d, 1H, J = 7Hz), 4.16 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz), 4.47 (dd, 1H, J = 7Hz, 10Hz), 4.54 (d, 1H, J = 13Hz), 4.73 (d, 1H, J = 13Hz),

 4.91 (t, 1H, J = 8Hz), 4.97 (d, 1H, J = 8Hz), 5.ll (s, 1H), 5.64 (d, 1H, J = 7Hz), 7.34 (d, 2H, J = 6Hz), 7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz),

8, ll (d, 2H, J = 8Hz), 8.57 (d, 2H, J = 6Hz)

Step 2: 13-O-[(2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, 0- (4-methoxybenzylidene) -3-phenylisoselinyl ]-10- deacetyl -10- 0-(4-pyridylmethyl) -7-0- triethylsilylpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 2 of Example 20 to give the title compound as a colorless amorphous solid.

■ H-NMRCCDCh / TMS) δ (ppm):

 0.49-0.53 (m, 6H), 0.91 (t, 9H, J = 8Hz), 1.06 (s, 9H), 1.19 (s, 3H), 1.23 (s, 3H), 1.54 (br, 3H), 1.64 ( s, 3H), 1.78 (br, 3H), 1.85-1.90 (m, 1H),

2.05-2.21 (m, 2H), 2.39-2.48 (m, 1H), 3.70 (d, 1H, J = 7Hz), 3.77 (s, 3H),

4.09 (d, 1H, J = 8Hz), 4.22 (d, 1H, J = 8Hz), 4.33 (dd, 1H, J = 7Hz, 10Hz),

4.48 (d, 1H, J = 13Hz), 4.57 (s, 1H), 4.60 (d, 1H, J = 13Hz), 4.84 (d, 1H, J = 8Hz), 4.96 (s, 1H), 5.40 (br , 1H), 5.62 (d, 1H, J = 7Hz), 6.10 (br, 1H), 6.39 (br, 1H), 6.93 (d, 2H, J = 9Hz), 7.31-7.50 (m, 11H), 7.62 (t, 1H, J = 8Hz),

8.03 (d, 2H, J = 8Hz), 8.59 (d, 2H, J = 6Hz)

Step 3: 13-0-CC2R, 3S) -N- (tert-butoxycarbonyl) -2,3-N, 0- (4-methoxybenzylidene) -3-phenylisoselinyl] -10- Deacetyl -10- 0- (4-pyridylmethyl)

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 3 of Example 20 to give the title compound as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) <5 (ppm):

 1.05 (s, 9H), 1.21 (s, 3H), 1.23 (s, 3H), 1.40 (s, 3H), 1.65 (s, 3H),

1.75 (br, 3H), 1.79 (m, 1H), 2.05-2.24 (m, 2H), 2.45-2.53 (m, 1H),

3.72 (d, 1H, J = 7Hz), 3.79 (s, 3H), 4.09 (d, 1H, J = 8Hz), 4.13 (dd, 1H, J = 7Hz, 10Hz), 4.22 (d, 1H, J = 8Hz), 4.54 (d, 1H, J = 14Hz),

4.55 (s, lH), 4.70 (d, 1H, J = 14Hz), 4.85 (d, 1H, J = 8Hz), 4.94 (s, 1H),

5.41 (br, 1H), 5.63 (d, 1H, J = 7Hz), 6.12 (br, 1H), 6.37 (br, 1H),

6.92 (d, 2H, J = 8Hz), 7.29 (d, 2H, J = 5.5Hz), 7.41-7.43 (m, 7H),

7.48 (t, 2H, J = 8Hz), 7.62 (t, 1H, J = 8Hz), 8.02 (d, 2H, J = 8Hz),

8.56 (d, 2H, J = 5.5Hz)

Step 4: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-10-O- (4-pyridylmethyl) Battery III

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 4 of Example 20 to give the title compound as a colorless solid.

Melting point: 160-165 ° C

■ H-NMRCCDCla / TMS) δ (ppm):

 1.20 (s, 3H), 1.28 (s, 3H), 1.33 (s, 9H), 1.66 (s, 3H), 1.73 (s, 3H),

1.83-1.89 (m, 1H), 2.29 (d, 2H, J = 8Hz), 2.36 (s, 3H), 2.49-2.57 (m, 1H),

 3.83 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz), 4.25 (dd, 1H, J = 7Hz, 10Hz),

4.31 (d, lH, J = 8Hz), 4.60 (d, 1H, J = 14Hz), 4.65 (s, lH), 4.82 (d, 1H, J = 14Hz),

4.94 (d, 1H, J = 8Hz), 5.02 (s, lH), 5.27 (d, 1H, J = 10Hz), 5.44 (d, 1H, J = 10Hz),

5.69 (d, 1H, J = 7Hz), 6.22 (t, 1H, J = 8Hz), 7.27-7.39 (m, 7H), 7.50 (t, 2H, J = 8Hz), 7.61 (d, 2H, J = 8Hz), 8.10 (d, 2H, J = 8Hz), 8.48 (d, 2H, J = 6Hz)

IR (KBr): 3444, 3072, 2984, 2940, 1948, 1726, 1606 cm " ¹

MS-FAB: 899 (MH ⁺ )

Example 23

Step 1: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-10 -O- [2- (3-thiazolidino) ethyl] -7-0- Triethylsilyl paccatin III

 The compound obtained in Step 1 of Example 14 was reacted in the same manner as in Step 1 of Example 2, and then reacted in the same manner as in Step 2 of Example 2 using thiazolidine instead of morpholine to give the title compound. Obtained as a colorless amorphous solid.

'H-N RCCDC / TMS) δ (ppm):

 -0.30 (s, 3H), -0.09 (s, 3H), 0.52-0.62 (m, 6H), 0.75 (s, 9H),

0.96 (t, 3H, J = 7Hz), 1.20 (s, 3H), 1.23 (s, 3H), 1.31 (s, 9H), 1.68 (s, 3H),

1.90-1.93 (m, 1H), 1.91 (s, 3H), 2.13-2.21 (m, 1H), 2.35-2.54 (m, 2H),

2.56 (s, 3H), 2.68 (t, 2H, J = 6Hz), 2.91 (t, 2H.J = 6Hz), 3.09-3.22 (m, 2H),

3.62-3.64 (m, 2H), 3.84 (d, 1H, J = 7Hz), 4.11-4.20 (m, 3H), 4, 31 (d, 1H, J = 8Hz), 4.42 (dd, 1H.J = 7Hz, 10Hz), 4.54 (s, 1H), 4.95 (d, 1H, J = 8Hz), 5.34 (br, 1H), 5.41 (br, 1H), 5.67 (d, 1H, J = 7Hz), 6.33 ( t, 1H.J = 8Hz), 7.27-7.37 (m, 5H),

7.47 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz)

Step 2: 13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy -3-Phenylpropionyl] -10-deacetyl _10- 0- [2- (3-thiazolidino) ethyl] paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a colorless solid.

Melting point: 147-153. C

'H-NMRCCDCla / TMS) δ (ppm):

 1.20 (s, 3H), 1.21 (s, 3H), 1.35 (s, 9H), 1.68 (s, 3H), 1.78-1.85 (m, 1H),

1.87 (s, 3H), 2.28 (m, 2H), 2.36 (s, 3H), 2.51-2.59 (m, 1H),

 2.68 (t, 2H, J = 5.5Hz), 2.90 (t, 2H, J = 5.5Hz), 3.10-3.19 (m, 2H),

 3.66-3.70 (m, 1H), 3.77-3.80 (m, 1H), 3.85 (d, 1H, J = 7Hz), 4.12 (s, 2H),

4.17 (d, 1H, J = 8Hz), 4.21 (dd, 1H, J = 7Hz, 10Hz), 4.30 (d, 1H, J = 8Hz),

 4.62 (s, 1H), 4.94 (d, 1H, J = 8Hz), 5.10 (s, 1H), 5.25 (br, 1H),

 5.40 (d, 1H, J = 10Hz), 5.67 (d, 1H, J = 7Hz), 6.22 (t, 1H, J = 8Hz).

7.32-7.40 (m, 5H), 7.49 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz) IR (KBr): 3456, 2980, 2940, 1722, 1768, 1604, 1586 cm— ¹

MS-FAB: 923 (MH ⁺ )

Example 24

Step 1: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-10_O -(2-Hydroxshetil) -7-0- Triethylsilylpaccatin Π Ι

550 mg of the compound obtained in Step 1 of Example 14 and N-methylmorpholine-N- 180 m of the oxide was dissolved in a mixed solvent of 40 ml of acetone and 10 ml of water, and 5 mg of osmium tetroxide was added at room temperature, followed by stirring for 3 hours. Sodium sulfite was added, and anhydrous sodium sulfate was further added for 15 minutes. After stirring for 30 minutes, insolubles were removed and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 40 ml of methanol, and a solution of 219 mg of sodium metaperiodate in 10 ml of water was added dropwise under ice-cooling, followed by stirring for 1 hour. A saturated aqueous solution of ammonium chloride was added, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 20 ml of tetrahydrofuran, 48 mg of sodium borohydride was added, and the mixture was stirred under ice cooling for 15 minutes. 1N hydrochloric acid was added until foaming stopped, and the mixture was diluted with water and extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the obtained residue was purified by silica gel chromatography (elution solvent: ethyl acetate: hexane = 1: 2 (v / v)) to obtain 278 mg of the title compound as a colorless amorphous Obtained as a solid.

 'H-NMR (CDCl3A S) <5 (ppm):

 -0.30 (s, 3H), -0.10 (s, 3H), 0.53-0.63 (m, 6H), 0.75 (s, 9H),

0.96 (t, 3H, J = 7Hz), 1.21 (s, 3H), 1.25 (s, 3H), 1.31 (s, 9H), 1.69 (s, 3H), 1.90-1.93 (m, 1H), 1.91 ( s, 3H), 2.15-2.20 (m, 1H), 2.31-2.40 (m, 1H),

 2.45-2.53 (m, 1H), 2.56 (s, 3H), 2.92 (br, 1H), 3.54-3.58 (m, 1H),

 3.66-3.70 (m, 1H), 3.79 (2H), 4.19 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

 4.44 (dd, 1H, J = 7Hz, 10Hz), 4.53 (s, 1H), 4.95 (d, 1H, J = 8Hz), 5.01 (s, 1H), 5.33 (br, lH), 5.41 (br, lH ), 5.67 (d, 1H, J = 7Hz), 6.33 (t, 1H, J = 8Hz),

7.27-7.39 (m, 5H), 7.48 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 8.11 (d, 2H, J = 8Hz) Step 2: 13-0-[( 2R, 3S)-3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl -10-0- [2- (p- Toluenesulfonyloxy) ethyl] -7-0- Triethylsilylpaccatin III 260 mg of the compound obtained in the above step 2 and 0.067 ml of triethylamine are dissolved in 10 ml of methylene chloride, and 118 mg of tosylic anhydride is added at room temperature. Stir for 2 hours. The reaction solution was washed with a saturated aqueous solution of sodium bicarbonate and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (elution solvent: ethyl acetate: hexane = 1: 4 (v / v)) to give 257 mg of the title compound as a colorless amorphous Obtained as a crystalline solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 -0.30 (s, 3H),-0.08 (s, 3H), 0.52-0.60 (m, 6H), 0.75 (s, 9H),

0.94 (t, 3H, J = 7Hz), 1.10 (s, 3H), 1.16 (s, 3H), 1.31 (s, 9H), 1.66 (s, 3H),

1.87-1.90 (m, 1H), 1.89 (s, 3H), 2.10-2.19 (m, 1H), 2.32-2.40 (m, 1H),

2.45 (s, 3H), 2.45-2.49 (m, 1H), 2.55 (s, 3H), 3.66-3.69 (m, 1H),

3.77-3.80 (m, 2H), 4.12 (d, 1H, J = 8Hz), 4.16-4.24 (m, 2H), 4.30 (d, 1H, J = 8Hz), 4.41 (dd, 1H, J = 7Hz, 10Hz), 4.54 (s, 1H), 4.94 (d, 1H, J = 8Hz), 4.95 (s, 1H),

5.33 (br, lH), 5.42 (br, lH), 5.63 (d, 1H, J = 7Hz), 6.32 (t, 1H, J = 8Hz),

7.28-7.39 (m, 7H), 7.47 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 7.82 (d, 2H, J = 8Hz), 8.ll (d, 2H, (J = 8Hz)

Step 3: 13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3_phenylpropionyl] -10-deacetyl-10 -O- (2-Ethylethyl) -7-0- Triethylsilylpaccatin ΠΙ

 200 mg of the compound obtained in the above step 2 was dissolved in 5 ml of acetonitrile, 121 mg of sodium iodide was added, and the mixture was heated under reflux for 2 hours. The reaction solution was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin eye chromatography (developing solvent; ethyl acetate: hexane = 1: 4 (v / v)) to obtain 184 mg of the title compound as a colorless amorphous solid.

 'H-NMRCCDCh / TMS) δ (ppm):

 -0.30 (s, 3H),-0.09 (s, 3H), 0.56-0.61 (m, 6H), 0.75 (s, 9H),

0.97 (t, 3H, J = 7Hz), 1.22 (s, 3H), 1.26 (s, 3H), 1.31 (s, 9H), 1.68 (s, 3H), 1.89-1.92 (m, 1H), 1.90 ( s, 3H), 2.11-2.20 (m, 1H), 2.33-2.4 Km, 1H),

2.46-2.56 (m, 1H), 2.57 (s, 3H), 3.30-3.37 (m, 2H), 3.66-3.70 (m, 1H),

 3.82 (d, 1H, J = 7Hz), 3.85-3.88 (m, 1H), 4.19 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

4.44 (dd, 1H, J = 7Hz, 10Hz), 4.54 (s, 1H), 4.95 (d, 1H, J = 8Hz), 5.00 (s, 1H),

5.31 (br, 1H), 5.43 (br, 1H), 5.67 (d, lH, J = 7Hz), 6.34 (t, 1H, J = 8Hz),

7.28-7.37 (m, 5H), 7.47 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 8.ll (d, 2H, J = 8Hz) Step 4: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-10 -O- [2- (1-Imidazolyl) ethyl] -7-0- Triethylsilylpaccatin III

Method A

 184 mg of the compound obtained in the above step 3 was dissolved in 5 ml of acetonitrile, 20.4 mg of N-acetylimidazole was added thereto, and the mixture was sealed and stirred at 100 ° C for 24 hours. After allowing the reaction solution to cool, 2 ml of a saturated aqueous solution of sodium bicarbonate was added, and the mixture was stirred for 20 minutes. Ethyl acetate and a saturated sodium bicarbonate aqueous solution (20 ml) were added, and the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-layer chromatography (eluent: developing solvent; chloroform: methanol = 20: 1 (v / v)) to give the title compound (26.5 mg) as a colorless amorphous solid.

B method

 2.8 mg of sodium hydride was added to 0.5 ml of N, N-dimethylformamide, and 7.8 mg of imidazole was added under nitrogen, followed by stirring at 90 ° C for 30 minutes. Next, a solution prepared by dissolving 115 mg of the compound obtained in the above step 3 in 2 ml of Ν, Ν-dimethylformamide was added dropwise and stirred at the same temperature for 40 minutes. The reaction solution was poured into ice water, extracted with ethyl acetate, washed with water and saturated brine in that order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was developed and purified by silica gel thin-layer chromatography (developing solvent; black form: methanol = 20: 1 (v / v)) to obtain 35.5 mg of the title compound as a colorless amorphous solid. Was.

 ■ H-NMRCCDCh / TMS) δ (ppm):

 -0.30 (s, 3H),-0.10 (s, 3H), 0.48-0.59 (m, 6H), 0.75 (s, 9H),

0.93 (t, 3H, J = 7Hz), 1.09 (s, 3H), 1.13 (s, 3H), 1.30 (s, 9H), 1.68 (s, 3H),

1.88-1.94 (m, 1H), 1.85 (s, 3H), 2.09-2.19 (m, 1H), 2.32-2.38 (m, 1H),

2.44-2.49 (m, 1H), 2.56 (s, 3H), 3.66-3.73 (m, 1H), 3.79 (m, 2H),

 4.15-4.25 (m, 2H), 4.30 (d, 1H, J = 8Hz), 4.40 (dd, 1H, J = 7Hz, 10Hz), 4.52 (s, lH),

4.93 (s, 1H), 4.94 (d, 1H, J = 8Hz), 5.32 (br, lH), 5.42 (br, lH),

 5.65 (d, 1H, J = 7Hz), 6.28 (t, 1H, J = 8Hz), 7.04 (s, 1H), 7.ll (s, 3H),

7.26-7.39 (m, 5H), 7.47 (t, 2H, J = 8Hz), 7.57-7.60 (m, 2H), 8.10 (d, 2H, J = 8Hz) Step 5: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl -10-0- [2- (1 -Imidazolyl) ethyl]

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a colorless solid.

Melting point: 163-169. C

_{'H-NMR (CDC1 3 /} TS) δ (ppm):

 1. ll (s, 3H), 1.14 (s, 3H), 1.33 (s, 9H), 1.67 (s, 3H), 1.69 (s, 3H),

 1.85-1.90 (m, 1H), 2.25 (m, 2H), 2.33 (s, 3H), 2.45-2.54 (m, 1H), 3.60 (m, 1H),

3.77 (d, 1H, J = 7Hz), 3.93 (m, 1H), 4.10-4.24 (m, 4H), 4.27 (d, 1H, J = 8Hz),

 4.61 (s, lH), 4.86 (s, lH), 4.93 (d, 1H, J = 8Hz), 5.20 (br, 1H),

 5.55 (d, 1H, J = 10Hz), 5.63 (d, 1H, J = 7Hz), 6.17 (t, 1H, J = 8Hz), 6.97 (s, 1H), 7.02 (s, lH), 7.29-7.38 (m, 5H), 7.48 (t, 2H, J = 8Hz), 7.55 (s, 1H),

 7.60 (t, 1H, J = 8Hz), 8.08 (d, 2H, J = 8Hz)

 IR (KBr): 3444, 3120, 3072, 2980, 2940, 1724, 1604, 1586 cm "'

MS-FAB: 902 (MH ⁺ )

Example 25

10-O-aryl- 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4,10-dideacetyl-7-deoxy -4- 0- B Pionylbaccatin III

The compound obtained in Step 4 of Example 15 was reacted in the same manner as in Step 7 of Example 3 to give a title. The compound was obtained as a colorless solid.

 ■ H-NMRCCDCh / TMS) δ (ppm):

 1.20-1.25 (m, 9H), 1.34 (s, 9H), 1.69 (s, 3H), 1.80-1.82 (m, 1H), 1.84 (s, 3H), 2.28 (m, 2H), 2.54-2.65 (m, 3H), 3.30 (br, 1H), 3.85 (d, IH, J = 7Hz),

4.06 (dd, IH, J = 6Hz, 13Hz), 4.16-4. 21 (m, 3H), 4.31 (d, IH, J = 8Hz), 4.62 (s, IH),

4.89 (d, 1H, J = 8Hz), 5.03 (s, 1H), 5.22 (d, 1H, J = 10Hz), 5.24 (br, IH),

5.29-5.40 (m, 2H), 5.69 (d, IH, J = 7Hz), 5.89-5.99 (m, IH), 6.22 (t, IH, J = 8Hz ), 7.32-7.4 Km, 5H), 7.49 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz)

Example 26

: About 1: 10-0-aryl-10-deacetyl-7-dexoxypaccatin III 10-Decetyl-7-dexoxypaccatin III was reacted in the same manner as in Step 1 of Example 1 to obtain the title compound as a white solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 8.12 (d, J = 7.3Hz, 2H), 7.60 (t, J = 7.3Hz, 1H), 7.48 (t, J = 7.3Hz, 2H),

5.90-6.03 (m, 1H), 5.63 (d, J = 7.3Hz, 1H), 5.31 (d, J = 15.6Hz, 1H),

5.22 (d, J = 10.2Hz, 1H), 5.07 (s, lH), 4.96 (dd, J = 2.5Hz, 9.5Hz, 1H),

 4.89 (s, 1H), 4.31 (d, J = 8.3Hz, 1H), 4.20 (d, J = 8.3Hz, 1H), 4.06-4.18 (m, 2H),

3.87 (d, J = 7.3Hz, 1H), 2.33 (dd, J = 6.8Hz, 15.6Hz, 1H), 2.28 (s, 3H),

 2.24 (dd, J = 6.4Hz, 15.6Hz, 1H), 1.19-2.12 (m, 4H), 2.02 (s, 3H), 1.74 (s, 3H), 1.68 (s, 1H), 1.52 (dd, J = 4.0Hz, 12.0Hz, 1H), 1.16 (s, 3H), 1.07 (s, 3H)

Step 2: 10-0-aryl-10-deacetyl-7-deoxy-13-0-triethylsilyl paccatin III

 To a solution of 1.60 g of the compound obtained in the above step 1 in 24 ml of N, N-dimethylformamide was added 1.91 g of imidazole and 4.71 ml of triethylchlorosilane at room temperature, and the mixture was stirred for 25 hours. A saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate were added to the reaction mixture, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent; hexane: ethyl acetate = 5: 1 to 3: 1 (v / v)) to obtain 1.75 g of the title compound as a white solid. .

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 8.10 (d, J = 7.3Hz, 2H), 7.59 (t, J = 7.3Hz, 1H), 7.47 (t, J = 7.3Hz, 2H),

 5.90-6.04 (m, 1H), 5.61 (d, J = 7.3Hz, 1H), 5.30 (d, J = 16.9Hz, 1H),

 5.22 (d, J = 12.2Hz, 1H), 5.05 (s, 1H), 4.96 (dd, J = 2.5Hz, 9.5Hz, 1H),

4.95 (t, J = 9.8Hz, 1H), 4.31 (d, J = 8.3Hz, 1H), 4.20 (d, J = 8.3Hz, 1H),

 4.06-4.17 (m, 2H), 3.78 (d, J = 7.3Hz, 1H), 2.28 (s, 3H), 1.90-2.33 (m, 5H),

1.97 (s, 3H), 1.74 (s, 3H), 1.62 (s, 1H), 1.52 (dd, J = 4.9 Hz, 11.7 Hz, lH),

1.15 (s, 3H), 1.12 (s, 3H), 1.02 (t, J = 7.8Hz, 9H), 0.67 (q, J = 7.8Hz, 6H)

Step 3: 10-O-aryl-10-deacetyl-1-0-dimethylsilyl-7-deokin-1 3-0- Triethylsilylpaccatin III

 To a solution of 460 m of the compound obtained in the above step 2 in 9.0 ml of N, N-dimethylformamide was added 183 mg of imidazole and 300/1 of dimethylchlorosilane at 0 ° C, and the mixture was stirred for 20 minutes. A saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate were added to the reaction mixture, the layers were separated, and the water layer was extracted with ethyl acetate. The organic layers were combined, washed with saturated brine (20 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent; hexane: ethyl acetate = 3: 1 (v / v)) to obtain 465 mg of the title compound as a white solid.

_{'H-NMR (CDC1 3 /} TMS) <5 (ppm):

 8.10 (d, J = 7.3Hz, 2H), 7.58 (t, J = 7.3Hz, 1H), 7.47 (t, J = 7.3Hz, 2H),

 5.90-6.05 (m, 1H), 5.69 (d, J = 7.3Hz, 1H), 5.30 (d, J = 15.6Hz, 1H),

 5.21 (d, J = 10.5Hz, lH), 5.01 (s, 1H), 4.92-5.01 (m, 1H), 4.50-4.57 (m, 1H),

4.29 (d, J = 8.3Hz, 1H), 4.25 (d, J = 8.3Hz, 1H), 4.05-4.18 (m, 2H),

3.70-3.79 (m, 1H), 2.28 (s, 3H), 1.40-2.50 (m, 6H), 1.96 (s, 3H), 1.85 (s, 3H), 1.15 (s, 3H), 1.08 (s, 3H), 1.04 (t, J = 7.8Hz, 9H), 0.70 (q, J = 7.8Hz, 6H),

0.08 (d, J = 2.9Hz, 3H), -0.27 (d, J = 2.9Hz, 3H).

Step 4: 10-O-aryl-7-deoxy-4,10-dideacetyl-4-0-propionyl paccatin III

0 was added to a solution of 465 mg of the compound obtained in the above step 3 in 9.0 ml of tetrahydrofuran. At C, bis (2-methoxyethoxy) aluminum sodium hydride 65¾ (w / v) toluene solution 9401 was added, and the mixture was stirred for 2 hours. Ethyl acetate, aqueous sodium potassium tartrate solution and water were added to the reaction mixture, stirred for 15 minutes, separated, and the water eyebrows were extracted with ethyl acetate. The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was roughly purified using silica gel column chromatography (elution solvent: hexane: ethyl acetate = 4: 1 (v / v)) to obtain 240 mg of a crude product as a white solid. To a solution of 240 mg of the crude product in 6.0 ml of tetrahydrofuran was added -550 ml of a 1M solution of lithium bis (trimethylsilyl) amide in tetrahydrofuran at に て 48, and the mixture was stirred for 15 minutes. Ride 47.0 u \ was added and the mixture was stirred for 1 hour. A saturated aqueous solution of ammonium chloride and ethyl acetate were added to the reaction mixture, the layers were separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a residue of 285 m. To a solution of 285 mg of the obtained residue in 4.0 ml of pyridine was added 1.0 ml of pyridine hydrogen fluoride at 0 ° C, and the mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into a stirring mixture of ethyl acetate and ice water, separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was subjected to gel chromatography on silica gel (developing solvent; hexane: ethyl acetate = 1: 1 (v / v)) to obtain 37.0 mg of the title compound as a white solid.

_{'H-NMR (CDC1 3 /} TMS) 5 (ppm):

 8.13 (d, J = 7.3Hz, 2H), 7.60 (t, J = 7.3Hz, 1H), 7.47 (t, J = 7.3Hz, 2H),

5.85-6.05 (m, 1H), 5.63 (d, J = 7.3Hz, 1H), 5.30 (d, J = 17.lHz, 1H),

5.22 (d, J = 10.3Hz, lH), 5.07 (s, 1H), 4.92 (d, J = 9.3Hz, 1H), 4.88 (s, 1H),

4.82 (s, lH), 4.32 (d, J = 8.3 Hz, 1H), 4.20 (d, J = 8.3 Hz, 1H), 4.05-4.18 (m, 2H ),

3.87 (d, J = 7.3Hz, 1H), 2.52-2.76 (m, 2H), 1.50-2.40 (m, 7H), 2.02 (s, 3H),

1.74 (s, 3H), 1.07 (s, 3H), 1.09 (s, 3H), 1.10-1.40 (m, 3H)

Step 5: 10-0-aryl-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl ] -4, 10-Dideacetyl-7-dexoxy-4-0-propionylbaccatin 1 1 1

 The compound obtained in the above Step 4 and (3R, 4S) -1- (tert-butoxycarbonyl) -4- (2-furyl) -3- (triisopropylsilyloxy) azetidin-2-one were prepared in Example 3. The title compound was obtained as a colorless amorphous solid.

■ H-NMRCCDCh / TMS) δ (ppm):

8.13 (d, J = 7.3Hz, 2H), 7.57 (t, J = 7.3Hz.1H), 7.47 (t, J = 7.3Hz, 2H),

 7.40 (s, 1H), 6.37 (d, J = 2.5Hz, 1H), 6.27 (d, J = 2.5Hz, 1H), 6.15-6.25 (m, 1H ), 5.90-6.03 (m, 1H), 5.69 (d, J = 7.3Hz, 1H), 5.18-5.37 (m, 4H), 5.04 (s, 1H ),

 4.98 (s, 1H), 4.92 (d, J = 7.3Hz, 1H), 4.33 (d, J = 7.8Hz, 1H),

4.24 (d, J = 7.8Hz, 1H), 4.08-4.16 (n 2H), 3.80 (d, J = 7.3Hz, 1H), 2.75 (q, J = 7.3Hz, 2H), 2.18-2.45 (m, 2H), 1.95-2.12 (m, 2H), 1.88 (s.3H),

1.50-1.80 (m, 2H), 1.76 (s, 3H), 1.73 (s, 1H), 1.33 (s, 9H), 1.15-1.40 (m, 12H),

0.90-1.05 (m, 18H)

Step 6: 10-0-aryl- 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10 -Didecetyl -7- dexoxy -4- 0- propionylbaccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 7 of Example 3 to obtain the title compound as a colorless amorphous solid.

■ H-NMRCCDCh / TMS) δ (ppm):

8.15 (d, J = 7.8Hz, 2H), 7.60 (t, J = 7.8Hz, 1H), 7.49 (t, J = 7.8Hz, 2H),

7.44 (brs, 1H), 6.49 (dd, J = 1.9Hz, 2.9Hz, 1H), 6.44 (d, J = 2.9Hz, 1H),

 6.37 (t, J = 8.8Hz, 1H), 5.90-6.02 (m, 1H), 5.68 (d, J = 7.3Hz, 1H),

5.15-5.35 (m, 4H), 5.03 (s, 1H), 4.90 (dd, J = 2.2Hz, 9.5Hz, 1H),

 4.70 (d, J = 7.3Hz, 1H), 4.33 (d, J = 8.5Hz, 1H), 4.22 (d.J = 8.5H2, 1H),

4.07-4.17 (m, 2H), 3.77 (d, J = 7.3Hz, 1H), 3.39 (d, J = 5.9Hz, 1H),

 2.62-2.80 (m, 2H), 2.43 (dd, J = 9.3Hz, 15.lHz, 1H), 2.17-2.32 (m, 2H),

1.77-2.12 (m, 2H), 1.86 (s, 3H), 1.76 (s, 3H), 1.73 (s, lH),

1.54 (dd, J = 4.6Hz, 12.3Hz, 1H), 1.32 (s, 9H), 1.26 (s, 3H), 1.22 (s, 3H),

1.18-1.30 (m, 3H)

Step 7: 13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -3- (2-furyl)-

2-Hydroxypropionyl] -4,10-dideacetyl-7-deoxy-4-0-propionyl-10-O- (2-thiomorpholinoethyl) baccatin III

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 1 of Example 2, and then reacted in the same manner as in Step 2 of Example 2 using thiomorpholine instead of morpholine to obtain the above compound as a colorless solid. Was.

 'H-NMRCCDCh / TMS) <5 (ppm):

 8.15 (d, J = 7.8Hz, 2H), 7.60 (t, J = 7.8Hz, 1H), 7.49 (t, J = 7.8Hz, 2H),

 7.44 (brs, 1H), 6.49 (dd, J = 1.5Hz, 2.9Hz, 1H), 6.45 (d, J = 2.9Hz, 1H),

6.26 (t, J = 8.8Hz, 1H), 5.67 (d, J = 7.3Hz, 1H, 5.32 (d, J = 10.7Hz, 1H), 5.18 (d, J = 9.8Hz, IH), 5.03 (s, IH), 4.89 (dd, J = 2.2Hz, 9.6Hz, IH),

 4.71 (d, J = 2. OHz, IH), 4.33 (d, J = 8.3Hz, IH), 4.22 (d, J = 8.3Hz, 1H),

 3.77 (d, J = 7.3Hz, IH), 3.56-3.74 (m, 2H), 2.78-2.90 (m, 4H), 2.62-2.78 (m, 8H),

2.42 (dd, J = 9.3Hz, 15.lHz, 1H), 2.19-2.32 (m, 2H), 1.92-2.12 (m, 2H),

 1.89 (s, 3H), 1.75 (s, 3H), 1.73 (s, 1H), 1.54 (dd, J = 5.7Hz, 11.9Hz),

 1.32 (s, 9H), 1.21 (s, 3H), 1.17 (s, 3H), 1.18-1.32 (m, 3H)

Industrial applicability

 The following experimental examples show the antitumor effects of the compounds of the present invention.

Experimental example

Three types of tumor cells, P388, PC-6 and PC-12, respectively, P388 is 5.0 × 10 ² cells / 150 1 / ゥ ヱ (well), PC-6 is 5.0 ^× 10 ^s cells / 150/1 / ゥ ヱ, PC- 12 was seeded on a 96-microliter microplate at l.Ox10 ³ cells / 150 1 / μl, and P388 was added with 50 μl after 2 hours and the other two after 24 hours. Then, the cells were cultured for 3 days, and a 5 mg / ml solution of 1 ^ -cho [3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl-2H-tetrazolium bromide] was added. 20 1 / ゥ ヱ was added.

After 4 hours, the culture was removed, dimethyl sulfoxide was added at 150 1 / ml, and the absorbance was measured at 540 nm. The antitumor effect was the concentration of the drug that caused cell proliferation in the drug-added group to be 50% of that in the control group. GI ₅ . The values (ng / ml) are shown in Table 1.

 table 1

P388 PC-6 PC-12 Taxotere 1.18 1.16

 Example s 0.112 0.616 0.639 Example 3 0.385 0.609 Example 12 0.236 0.273

 Example 15 0.232 0.338 0.551 Example 180, 188 0.627 1.23

Example 26 0.421 0.0547 The compound of the present invention not only exhibits a strong antitumor effect but also has excellent water solubility, and the solubility of lm in water is as follows (our experimental data).

 Taxotere Approx.0.03 mg / m1

 Compound of Example 10 13.0 mg / m 1

Claims

The scope of the claims

 1. General formula (I)

[Where,

R ¹ is a phenyl group

 (The phenyl group may have, as a substituent, one or more groups selected from the group consisting of a halogen atom, an alkynole group and an alkoxyl group.)

 Means

R ² is an alkyl group, alkenyl group, alkyninole group, cycloalkyl group or alkoxyl group

 (These alkynole, alkenyl, alkynyl, cycloalkyl and alkoxyl groups include a halogen atom, a hydroxyl group, a carboxyl group, an alkoxynole group, an aryloxy group, a phenyl group, an amino group, an alkylamino group and an alkoxycarbonyl group. And a substituent selected from the group consisting of an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group.

Means

R ³ represents a hydroxyl group, a hydrogen atom or a halogen atom.

R ⁴ is an alkynole, alkenyl or alkynyl group (These alkyl groups, alkenyl groups or alkynyl groups include carboxyl group, alkoxyl group, aryloxy group, alkoxycarbonyl group, aryloxy group, cyano group, hydroxyl group, amino group, amino group, alkylamino group, acyl group, and acyl group. It may have one or more substituents selected from the group consisting of a lumino group, an acyloxy group, an alkoxycarbonylamino group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, an aryl group and a heterocyclic group. The aryl group and the heterocyclic group further include a carboxyl group, an alkyl group, an alkoxyl group, an aryloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, a cyano group, a hydroxyl group, an amino group, an alkylamino group, and an aminoalkyl group. , Sill group, Anruamino group, Ashiruokishi group, an alkoxycarbonyl § amino group, alkylthio O group, a group selected from alkylsulfinyl group consisting Le group and an alkylsulfonyl group which may have one or more as a substituent.)

Means

R ⁵ represents a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group.

R ⁶ represents a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group.

R ⁷ is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, or a heterocyclic group

 (These alkyl groups, alkenyl groups, alkynyl groups, cycloalkyl groups, aryl groups, or heterocyclic groups include halogen atoms, hydroxyl groups, carboxyl groups, alkyl groups, alkoxyl groups, aryloxy groups, phenyl groups, amino groups, and alkylamino groups. Group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group, and one or more groups selected from the group consisting of an acyloxy group as a substituent. Is also good.

R ⁸ is an alkyl group, aryl group or alkoxyl group

(These alkyl groups, aryl groups or alkoxyl groups include a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxyl group, an aryloxy group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, and an alkylaminoalkyl group. Groups, alkoxycarbonyl groups, aryloxycarbonyl groups, acyl groups, It may have one or more groups selected from the group consisting of a lumino group and an acyloxy group as substituents. )

Means ]

And a salt thereof.

2. The compound according to claim 1, wherein R ⁵ and R ⁶ are a fluorine atom, and a salt thereof.

3. The compound according to claim 1, wherein R ⁵ is a hydroxyl group, and R ⁶ is a hydrogen atom, and a salt thereof.

4. The compound according to claim 1, wherein R ⁵ is a hydroxyl group, and R ⁶ is a methyl group, and a salt thereof.

5. The compound according to claim 1, wherein R ⁸ is a fuunyl group, and a salt thereof.

6. The compound according to claim 1, wherein R ⁸ is a tertiary butoxy group, and a compound thereof.

7. The compound according to claim 1, wherein R ^{7 is a} phenyl group, and a salt thereof.

8. The compound according to claim 1, wherein R ⁷ is a heterocyclic group, and a salt thereof.

9. The compound according to claim 1, wherein R ⁷ is a monocyclic heterocyclic group, and a compound thereof.

10. The compound according to claim 1, wherein R ⁷ is a monocyclic 5- or 6-membered heterocyclic group, and a salt thereof.

1 1. A claim wherein R ⁷ is a monocyclic 5- or 6-membered ring, and is a heterocyclic group containing one oxygen atom, nitrogen atom or sulfur atom as a ring structure atom. 2. The compound according to item 1, and a salt thereof.

1 2. R ⁷ is a monocyclic 5- or 6-membered ring, and is an unsaturated heterocyclic group containing one oxygen atom, nitrogen atom or sulfur atom as a ring structure constituent atom The compound according to claim 1, and a salt thereof.

13. The compound according to claim 1, wherein R ^{7 is a} furyl group, a pyridyl group or a pyrrolyl group, and a salt thereof.

14. The compound according to claim 1, wherein R ⁷ is a 2-methyl-1-proenyl group, and a salt thereof. 3779

15. The compound according to claim 1, wherein R is an alkyl group having 1 to 6 carbon atoms, and a salt thereof.

16. The compound according to claim 1, wherein R ² is an alkoxyl group having 1 to 6 carbon atoms, and a salt thereof.

17. The compound according to claim 1, wherein R ² is a cycloalkyl group having 3 to 6 carbon atoms, and a salt thereof.

18. The compound according to claim 1, wherein R ² is a methyl group, an ethyl group or a propyl group, and a salt thereof.

1 9. R ² Chikarakume. The compounds and salts thereof of claims claim 1 wherein a butoxy group or an ethoxy group.

20. The compound according to claim 1, wherein R ² is a cyclopropyl group, and a salt thereof.

2. The compound according to claim 1, wherein R ⁴ is an alkenyl group, and a salt thereof.

22, The compound according to claim 1, wherein R ⁴ is an aryl group, and a salt thereof.

23. The compound according to claim 1, wherein R ⁴ is an alkyl group, and a salt thereof.

24. The compound according to claim 1, wherein R ⁴ is an alkyl group having an alkylamino group as a substituent, and a salt thereof.

 25. The compound according to claim 1, wherein R is an alkyl group having a heterocyclic group as a substituent, and a salt thereof.

2 6. R ⁴ is a substituent of the formula

One N X

(X means oxygen atom, sulfur atom, S = 0, CH ₂ , CH—Y, ΝΗ or Ν—Υ, and Υ means an alkyl group.)