Lipase-catalysed kinetic resolution in organic solvents: an approach to enantiopure α-methyl-β-alanine esters

Abstract

The Candida antarctica lipase A (CAL-A) and B (CAL-B)-catalysed resolutions of α-methyl-β-alanine ethyl ester 1 with neat ethyl and butyl butanoates and with 2,2,2-trifluoroethyl butanoate in organic solvents were studied, as were the alcoholyses in neat butanol and with methanol (0.8 M) in diisopropyl ether. The two enzymes, which display opposite ( S for CAL-A and R for CAL-B) and low enantioselectivities ( E=7–10), allowed the preparation of the two enantiomers in a two-step resolution protocol. The R enantiomer (ee=97%) was first separated as its Boc-protected derivative from the CAL-A-catalysed resolution mixture of ( R)- 1 and the enantiomerically enriched N-butanoylated counterpart. The enantiopurification of the latter gave the S enantiomer (ee=96%) in the following CAL-B-catalysed ‘interesterification’ in butyl butanoate.