Enzymes in organic synthesis, 25 . Lipase‐catalyzed sequential esterification of (±)‐2‐methylbutanedioic anhydride — a biocatalytical access to an enantiomerically pure 1‐monoester of ( S )‐2‐methylbutanedioic acid

The preparation of enantiomerically pure 1‐(2‐methylpropyl) 4‐hydrogen ( S )‐2‐methylbutanedioate ( ent ‐ 3 ) by an enzyme‐catalyzed sequential esterification of (±)‐2‐methylbutanedioic anhydride ( rac ‐ 1 ) demands two different enzymes. Lipozyme, a lipase from Mucor miehei , was used for the alcoholysis of rac ‐ 1 to a mixture of the isomeric monoesters 2 / ent ‐ 2 and 3 / ent ‐ 3 , whereas Novozym 435, a lipase from Candida antarctica , was required for the enantioselective conversion of a mixture of 3 and ent ‐ 3 into the easily separable neutral diester 4 and the acidic monoester ent ‐ 3 , which thus was obtained in a yield of 26% with an enantiomeric excess of 99%. ent ‐ 3 was reduced by LiBH 4 to ( S )‐3‐methylbutan‐4‐olide ( ent ‐ 10 ), a versatile chiral intermediate.