Patent ID: 6211412
Filing Date: 2001-04-03
Classification: C07B,C07C,C07D,C07F

Abstract:
A method of synthesizing an epothilone precursor of the formula ##STR24##where n.sub.1 is an integer from 0-4, R.sub.4 is selected from the group consisting of H, C1-C10 straight and branched chain alkyl groups, substituted and unsubstituted benzyl groups, and C1-C10 alkoxy groups, R.sub.5 and R.sub.6 are each individually and respectively selected from the group consisting of H, substituted and unsubstituted aryl and heterocyclic groups, C1-C10 straight and branched chain alkyl groups, and substituted and unsubstituted benzyl groups, R.sub.7 is H or straight or branched chain C1-C10 alkyl groups, and P' is a protective group, comprising the steps of:providing a .beta.-keto ester of the formula ##STR25##where n.sub.1, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and P' are as defined above, and T is an alkyl group;preferentially hydrogenating the C3 keto group of said .beta.-keto ester to form the corresponding hydroxyester by reacting the .beta.-keto ester with a hydrogenating agent in the presence of an asymmetric organometallic molecular catalyst comprising a metal atom or ion having one or more chiral ligands coupled thereto; andconverting the hydroxyester to said epothilone precursor.