Method for preparation of taxol

Claim 2

A β-lactam of the formula: wherein R₁ is aryl, substituted aryl, alkyl, alkenyl, or alkynyl; R₂ is hydrogen, ethoxyethyl, 2,2,2-trichloroethoxy­methyl or other hydroxyl protecting group; and R₃ is aryl, substituted aryl, alkyl, alkenyl, or alkynyl.

Claim 3

The compound of claim 1 wherein R₁ is phenyl, substituted phenyl, or aryl; R₂ is ethoxyethyl, or 2,2,2-­trichloroethoxymethoxy; and R₃ is phenyl, substituted phenyl, or aryl.

Claim 4

A β-lactam of the formula: wherein R₂ is a hydroxyl protecting group.

Claim 5

A β-lactam of the formula: wherein R₂ is a hydroxyl protecting group.

Claim 6

The compound of any one of claims 1 to 3 wherein R₂ is selected from the group consisting of acetals, ethers, esters, and carbonates.

Claim 7

The compound of any one of claims 1 to 4 wherein R₂ is ethoxyethyl.

Claim 8

A process for the preparation of a taxol intermediate comprising contacting an alcohol with a β-­lactam having the formula: wherein R₁ is aryl, substituted aryl, alkyl, alkenyl, or alkynyl, R₂ is a hydroxyl protecting group and R₃ is aryl, substituted aryl, alkyl, alkenyl, or alkynyl, the contacting of said alcohol and β-lactam being carried out in the presence of a sufficient amount of an activating agent under effective conditions to cause the β-­lactam to react with the alcohol to form a β-amido ester which is suitable for use as an intermediate in the synthesis of taxol.

Claim 9

A process for the preparation of a taxol intermediate comprising contacting an alcohol with a β-­lactam having the formula: wherein R₁ is aryl, substituted aryl, alkyl, alkenyl, or alkynyl, R₂ is a hydroxyl protecting group and R₃ is aryl, substituted aryl, alkyl, alkenyl, or alkynyl, the contacting of said alcohol and β-lactam being carried out in the presence of a sufficient amount of an activating agent under effective conditions to cause the β-­lactam to react with the alcohol to form a β-amido ester which is suitable for use as an intermediate in the synthesis of taxol.

Claim 10

A process for the preparation of taxol which comprises preparing a taxol intermediate by a process according to claim 6 and converting said intermediate to taxol.

Claim 11

The process of claim 6 or claim 7 wherein the hydroxyl protecting group is selected from acetals, ethers, esters, and carbonates.

Claim 12

The process of any one of claims 6 to 8 wherein R₁ is aryl, or substituted aryl; R₂ is ethoxyethyl or 2,2,2-­trichloroethoxymethyl; and R₃ is aryl or substituted aryl.

Claim 13

The process of any one of claims 6 to 9 wherein R₂ is ethoxyethyl.

Claim 14

A process for the preparation of a taxol having the formula: wherein A and B are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or A and B together form an oxo; L and D are independently hydrogen or hydroxy or lower alkanoyloxy, alkenoyloxy, alkynoyloxyl, or aryloyloxy; E and F are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or; E and F together form an oxo; G is hydrogen or hydroxy or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or G and M together form an oxo or methylene or G and M together form an oxocyclopropyl ring or M and F together form an oxocyclobutyl ring; J is hydrogen, hydroxy, or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or I is hydrogen, hydroxy, or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy; or I and J taken together form an oxo; and K is hydrogen, hydroxy or lower alkoxy, alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy; and P and Q are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or P and Q together form an oxo; and S and T are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or S and T together form an oxo; and U and V are independently hydrogen or lower alkyl, alkenyl, alkynyl, aryl, or substituted aryl; and W is aryl, substituted aryl, lower alkyl, alkenyl, or alkynyl, comprising: contacting a β-lactam of the formula: wherein R₁ is phenyl, substituted phenyl, aryl, alkyl, alkenyl, or alkynyl; R₂ is a hydroxyl protecting group; and R₃ is phenyl, substituted phenyl, aryl, alkyl, alkenyl, or alkynyl; with an alcohol of the formula: wherein said A, B, D, E, F, G, I, J, K, L, M, P and Q are as defined above, the contacting of said β-lactam and said alcohol being carried out in the presence of a sufficient amount of an activating agent under effective conditions to cause the β-lactam to react with the alcohol to form a β-­amido ester which is suitable for use as an intermediate in the synthesis of taxol, and converting said intermediate to taxol.

Claim 15

A process for the preparation of a taxol having the formula: wherein A and B are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or A and B together form an oxo; L and D are independently hydrogen or hydroxy or lower alkanoyloxy, alkenoyloxy, alkynoyloxyl, or aryloyloxy; E and F are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or; E and F together form an oxo; G is hydrogen or hydroxy or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or G and M together form an oxo or methylene or G and M together form an oxocyclopropyl ring or M and F together form an oxocyclobutyl ring; J is hydrogen, hydroxy, or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or I is hydrogen, hydroxy, or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy; or I and J taken together form an oxo; and K is hydrogen, hydroxy or lower alkoxy, alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy; and P and Q are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or P and Q together form an oxo; and S and T are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or S and T together form an oxo; and U and V are independently hydrogen or lower alkyl, alkenyl, alkynyl, aryl, or substituted aryl; and W is aryl, substituted aryl, lower alkyl, alkenyl, or alkynyl, comprising: contacting a β-lactam of the formula: wherein R₁ is phenyl, substituted phenyl, aryl, alkyl, alkenyl, or alkynyl; R₂ is a hydroxyl protecting group; and R₃ is phenyl, substituted phenyl, aryl, alkyl, alkenyl, or alkynyl; with an alcohol of the formula: wherein said A, B, D, E, F, G, I, J, K, L, M, P and Q are as defined above, the contacting of said β-lactam and said alcohol being carried out in the presence of a sufficient amount of an activating agent under effective conditions to cause the β-lactam to react with the alcohol to form a β-­amido ester which is suitable for use as an intermediate in the synthesis of taxol, and converting said intermediate to taxol.

Claim 16

The process of any one of claims 6 to 11 wherein the alcohol has the formula: wherein R₄ is a hydroxyl protecting group.

Claim 17

The process of claim 12 wherein R₄ is selected from ethers, esters, carbonates and silyl groups.

Claim 18

The process of claim 12 or 13 wherein R₄ is ethoxyethyl, trimethyl silyl or triethyl silyl.

Claim 19

The process of any one of claims 6 to 14 wherein said R₁ is phenyl and said R₃ is phenyl.

Claim 20

The process of any one of claims 6 to 15 wherein the activating agent is a tertiary amine.

Claim 21

The process of claim 16 wherein the activating agent is triethyl amine, diisopropyl ethyl amine, pyridine, N-methyl imidazole, or 4-dimethylaminopyridine.