A synthesis of (-)-sitophilate by utilizing yeast-mediated reduction of an enol ester

The microbial reduction of 1′-ethylpropyl 2-methyl-3-oxopentanoate, a β-keto ester possessing bulky substituent, as well as the corresponding enol ester was examined. Epimeric mixture of hydroxy ester, containing (2S,3S-isomer as the major product (92%e.e., 43%d.e.) was obtained via the reduction of enol ester with growing cells of Pichia farinosa IAM 4682 in 63% yield. The resulting β-hydroxy ester was converted to (2S,3R)-isomer (88%e.e., 96%d.e.), of which e.e. was further enhanced by the lipase-catalyzed partial hydrolysis of the corresponding chloroacetate to give (-)-sitophilate, (99%e.e., 98%d.e.) an aggregation pheromone of Sitophillus granarius L.