US5015744A
Expired / Lapsed
US
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Method for preparation of taxol using an oxazinone
Assignee: Florida State University
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Filing: 1989-11-14
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Granted: 1991-05-14
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Expires: 2009-11-14
Abstract
Abstract Process for the preparation of a taxol intermediate comprising contacting an alcohol with an oxazinone having the formula: ##STR1## wherein R 1 is aryl, substituted aryl, alkyl, alkenyl, or alkynyl; R 2 is hydrogen, ethoxyethyl, 2,2,2-trichloroethoxymethyl or other hydroxyl protecting group; and R 3 is aryl, substituted aryl, alkyl, alkenyl, or alkynyl; the contacting of said alcohol and oxazinone being carried out in the presence of a sufficient amount of an activating agent under effective conditions to cause the oxazinone to react with the alcohol to form a β-amido ester which is suitable for use as an intermediate in the synthesis of taxol.
Inventors
- 👤 Robert A. Holton
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 02:24
CPC Classifications
C; C07; C07D; C07D305/00; C07D305/14; C07C; C07C233/00; C07C233/64; C07C233/81; C07C233/82; C07C233/87; C07D265/00; C07D265/04; C07D265/06; C07C2603/00; C07C2603/56; C07C2603/58; C07C2603/76; C07C2603/84; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
347 words
A process for the preparation of a taxol having the formula: ##STR13## 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, alkynoyloxy, or aryloyloxy; E and F are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or; E and F together from 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 oxirane or M and F together form an oxetane; 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 an oxazinone of the formula: ##STR14## wherein R 1 is aryl, substituted aryl, alkyl, alkenyl, or alkynyl; R 2 is hydrogen, ethoxyethyl, 2,2,2-trichloroethoxymethyl or other hydroxyl protecting group; and R 3 is aryl, substituted aryl, alkyl, alkenyl, or alkynyl; with an alcohol of the formula: ##STR15## wherein said A, B, D, E, F, G, I, J, K, L, M, P and Q are as defined above, the contacting of said oxazinone and said alcohol being carried out in the presence of a sufficient amount of an activating agent to cause the oxazinone 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 2
Dependent Claim
347 words
A process for the preparation of a taxol having the formula: ##STR13## 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, alkynoyloxy, or aryloyloxy; E and F are independently hydrogen or lower alkanoyloxy, alkenoyloxy, alkynoyloxy, or aryloyloxy or; E and F together from 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 oxirane or M and F together form an oxetane; 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 an oxazinone of the formula: ##STR14## wherein R 1 is aryl, substituted aryl, alkyl, alkenyl, or alkynyl; R 2 is hydrogen, ethoxyethyl, 2,2,2-trichloroethoxymethyl or other hydroxyl protecting group; and R 3 is aryl, substituted aryl, alkyl, alkenyl, or alkynyl; with an alcohol of the formula: ##STR15## wherein said A, B, D, E, F, G, I, J, K, L, M, P and Q are as defined above, the contacting of said oxazinone and said alcohol being carried out in the presence of a sufficient amount of an activating agent to cause the oxazinone 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 3
Dependent Claim
74 words
The process of claim 1 wherein aryl is C 6-15 aryl, substituted aryl is C 6-15 substituted aryl, the substituents of which are selected from alkanoxy, hydroxy, halogen, alkyl, aryl, alkenyl, acyl, acyloxy, nitro, amino, and amido, alkyl is C 1-15 alkyl, alkenyl is C 2-15 alkenyl and alkynyl is C 2-15 alkynyl, alkanoyloxy is C 1-15 alkanoyloxy, alkenoyloxy is C 2-15 alkenoyloxy, alkynoyloxy is C 2-15 alkynoyloxy, and aryloyloxy is C 6-15 aryloyloxy.
Claim 4
Dependent Claim
21 words
The process of claim 1 wherein said alcohol has the following formula: ##STR16## wherein R 4 is a hydroxyl protecting group.
Claim 5
Dependent Claim
17 words
The process of claim 3 wherein R 4 is selected from ethers, esters, carbonates and silyl groups.
Claim 6
Dependent Claim
15 words
The process of claim 3 wherein R 4 is ethoxyethyl, trimethyl silyl or triethyl silyl.
Claim 7
Dependent Claim
17 words
The process of claim 3 wherein said R 1 is phenyl and said R 3 is phenyl.
Claim 8
Dependent Claim
20 words
The process of claim 6 wherein said activating agent is triethyl amine, diisopropyl ethyl amine, pyridine, N-methyl imidazole, or 4-dimethylaminopyridine.
Claim 9
Dependent Claim
20 words
The process of claim 1 wherein said other hydroxyl protecting group is selected from ethers, esters, carbonates and silyl groups.
Claim 10
Dependent Claim
13 words
The process of claim 1 where said activating agent is a tertiary amine.
Claim 11
Dependent Claim
20 words
The process of claim 1 wherein said activating agent is triethyl amine, diisopropyl ethyl amine, pyridine, N-methyl imidazole, or 4-dimethylaminopyridine.
Claim 12
Dependent Claim
10 words
The process of claim 1 wherein R 1 is phenyl.
Claim 13
Dependent Claim
13 words
The process of claim 1 wherein R 1 and R 3 are phenyl.
Claim 14
Dependent Claim
10 words
The process of claim 12 wherein R 4 is ethoxyethyl.
Claim 15
Dependent Claim
10 words
The process of claim 1 wherein R 2 is ethoxyethyl.
Claim 16
Dependent Claim
72 words
A process for the preparation of taxol comprising reacting an oxazinone of the formula ##STR17## wherein R 2 is a hydroxyl protecting group and Ph is phenyl, with an alcohol of the formula ##STR18## wherein R 4 is a hydroxyl protecting group, in the presence of a tertiary amine activating agent to form an intermediate, and converting the intermediate to taxol by hydrolyzing the R 2 and R 4 hydroxyl protecting groups.
Claim 17
Dependent Claim
72 words
A process for the preparation of taxol comprising reacting an oxazinone of the formula ##STR17## wherein R 2 is a hydroxyl protecting group and Ph is phenyl, with an alcohol of the formula ##STR18## wherein R 4 is a hydroxyl protecting group, in the presence of a tertiary amine activating agent to form an intermediate, and converting the intermediate to taxol by hydrolyzing the R 2 and R 4 hydroxyl protecting groups.
Claim 18
Dependent Claim
21 words
The process of claim 15 wherein R 2 and R 4 are independently selected from ethers, esters, carbonates and silyl groups.
Claim 19
Dependent Claim
21 words
The process of claim 15 wherein R 2 and R 4 are independently selected from ethoxyethyl, trimethyl silyl or triethyl silyl.
Claim 20
Dependent Claim
22 words
The process of claim 15 wherein the tertiary amine activating agent is triethyl amine, diisopropyl ethyl amine, pyridine, N-methyl imidazole, or 4-dimethylaminopyridine.
Claim 21
Dependent Claim
18 words
The process of claim 15 wherein said reacting step is carried out at a temperature of 25° C.
References Cited (Backward Citations)
EP0253739A1
Cited
US4814470A
Cited
US4857653A
Cited
EP0253738B1
Cited
EP0336841A1
Cited
EP0336840A1
Cited
US4924012A
Cited
US4924011A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-05-13 | 1994-11-12 | 1995-05-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-05-13 | 1998-11-12 | 1999-05-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-05-13 | 2002-11-12 | 2003-05-14 | $7700.00 | Window Closed / Lapsed |