Chemo-enzymatic synthesis of chiral 2-substituted succinic acid derivatives

Abstract Prochiral discrimination by the biocatalyst Alcalase ® , an enzyme preparation of subtilisin Carlsberg, was used to effect enantio- and regioselective monohydrolysis of a variety of ( RS )-2-substituted succinate diesters to afford the corresponding half esters in modest to excellent enantiomeric excesses (>99%). Exploitation of malonate chemistry, as well as recycling of the unhydrolyzed isomer from the enantioselective hydrolysis, has resulted in a process which is both practical and economical.