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 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.
Claims16
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:
- or where R1 is in the trans position relative to t-butyl group in both formulas IIa and IIb:
- 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 which is a microbial amidase, or a microorganism which produces the amidase, 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 for the resolution of a mixture comprising the enantiomers of formulas Ia and Ib , wherein R1 is the cis position relative to the t-butyl group in both formulas Ia and Ib:
- 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 which is a microbial amidase or a microorganism which produces the amidase, 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.
Dependencies are inferred from the claim text.