Enzymatic resolution of t-butyl taxane derivatives
AssigneeBristol-Myers Squibb Company
InventorRamesh N. Patel
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Abstract
A method for the resolution of a mixture of the cis or trans enantiomers of a compound of the formula 1 wherein R1 is —O—C(O)alkyl, —O—C(O)aryl or —O—C(O)cycloalkyl by contacting the mixture with a carboxylic ester hydrolase enzyme which catalyzes the stereoselective hydrolysis of the mixture and the use of such enantiomers to produce antitumor compounds which are especially suitable for oral administration.
Claims14
A method for the resolution of a mixture comprising the enantiomers of formulas Ia and Ib , wherein R1 is the cis position relative to t-butyl group in both formulas Ia and Ib:
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- or where R1 is in the trans position relative to t-butyl group in both formulas IIa and IIb:
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- where
- R1 is —O—C(O) alkyl, —O—C(O) aryl or —O—C(O) cycloalkyl;
- comprising the steps of (a) contacting said mixture with a carboxylic ester hydrolase enzyme, wherein said enzyme catalyzes the stereoselective hydrolysis of said mixture to provide a mixture of two compounds in which in one compound R1 is —O—C(O) alkyl, —O—C(O)-aryl or —O—C(O) cycloalkyl and in the other compound R1 is hydroxy, and (b) recovering one or both of said compounds.
A method of preparing a compound of formula III
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- wherein:
- R1 is —O—C(O) alkyl, —O—C(O) aryl or —O—C(O) cycloalkyl;
- and
- R2 is CH3C(O)O—.
- comprising reacting a compound selected from formulas Ia, Ib, IIa and IIb.
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- where
- R1 is —O—C(O) alkyl, —O—C(O)-aryl or —O—C(O) cycloalkyl;
- with a compound of formula IV
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- wherein R2 is CH3C(O)O—
- and R4 is a protecting group
- and removing the R4 group to form a compound of formula III.
Dependencies are inferred from the claim text.