Method for preparation of taxol using an oxazinone
AssigneeFlorida State University
InventorRobert A. Holton
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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, heteroaryl, alkyl, alkenyl, alkynyl or OR.sub.7 wherein R.sub.7 is alkyl, alkenyl, alkynyl, aryl or heteroaryl; R.sub.2 and R.sub.5 are independently selected from hydrogen, alkyl alkenyl, alkynyl, aryl, heteroaryl, and OR.sub.8 wherein R.sub.8 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or hydroxyl protecting group; and R.sub.3 and R.sub.6 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl and heteroaryl.
Claims14
A process for the preparation of taxol which comprises contacting an alcohol with an oxazinone of the formula:
- ##STR16## wherein R.sub.1 is aryl, alkyl, alkenyl, alkynyl or --OR.sub.7 wherein R.sub.7 is alkyl, alkenyl, alkynyl, or aryl;
- R.sub.8 is hydrogen, ethoxyethyl, 2,2,2-trichloroethoxymethyl or other hydroxyl protecting group;
- and R.sub.3 is 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 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 a taxol having the formula:
- ##STR18## 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 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 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 hydroben 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;
- and
- W is aryl, lower alkyl, alkenyl, alkynyl, alkoxy, or aryloxy, comprising:
- contacting an oxazinone of the formula:
- ##STR19## wherein R.sub.1 is aryl, alkyl, alkenyl, alkynyl or --OR.sub.7 wherein R.sub.7 is alkyl, alkenyl, alkynyl, or aryl;
- R.sub.2 and R.sub.5 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, arly, and --OR.sub.8 wherein R.sub.8 is alkyl, alkenyl, alkynyl, aryl, or hydroxyl protecting group;
- and R.sub.3 and R.sub.6 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, and aryl;
- with an alcohol of the formula;
- ##STR20## 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.
Dependencies are inferred from the claim text.