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 es terification of (+/-)-2-methyIbutanedioic anhydride (rac-1) demands tw o different enzymes. Lipozyme, a lipase from Mucor miehei, was used fo r the alcoholysis of rac-1 to a mixture of the isomeric monoesters 2/e nt-2 and 3/ent-3, whereas Novozym 435, a lipase from Candida antarctic a, was required for the enantioselective conversion of a mixture of 3 and ent-3 into the easily separable neutral diester 4 and the acidic m onoester ent-3, which thus was obtained in a yield of 26% with an enan tiomeric excess of 99%. ent-3 was reduced by LiBH4 to (S)-3-methylbuta n-4-olide (ent-10), a versatile chiral intermediate.