Studies on the synthesis of DNA-damaging part of leinamycin: regioselectivity in Ti(O iPr) 4 mediated opening of hydroxy epoxides with carboxylic acids

Abstract

The preparation of the key intermediate in the synthesis of the DNA damaging fragment of the anticancer antibiotic leinamycin starting from geraniol is described. The synthetic sequence involves the building of a quaternary asymmetric center through kinetic resolution through Sharpless epoxidation followed by the regioselective opening of the resultant enantiomerically pure hydroxyepoxide and intramolecular Wittig–Horner olefination.