Method for preparation of taxol using an oxazinone
AssigneeFlorida State University
InventorRobert A. Holton
Life of this patent
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Abstract
Process for the preparation of a taxol intermediate comprising contacting an alcohol with an oxazinone having the formula: ##STR1## wherein R.sub.1 is aryl, substituted aryl, alkyl, alkenyl, or alkynyl; R.sub.2 is hydrogen, ethoxyethyl, 2,2,2-trichloroethoxymethyl or other hydroxyl protecting group; and R.sub.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 .beta.-amido ester which is suitable for use as an intermediate in the synthesis of taxol.
Claims19
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.sub.1 is aryl, substituted aryl, alkyl, alkenyl, or alkynyl;
- R.sub.2 is hydrogen, ethoxyethyl, 2,2,2-trichloroethoxymethyl or other hydroxyl protecting group;
- and R.sub.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 .beta.-amido ester which is suitable for use as an intermediate in the synthesis of taxol, and converting said intermediate to taxol.
A process for the preparation of taxol comprising reacting an oxazinone of the formula ##STR17## wherein R.sub.2 is a hydroxyl protecting group and Ph is phenyl, with an alcohol of the formula ##STR18## wherein R.sub.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.sub.2 and R.sub.4 hydroxyl protecting groups.
Dependencies are inferred from the claim text.