Chemo-Enzymatic Synthesis and Determination of the Absolute Configuration of Both Enantiomers of Methyl trans-5-Oxo-2-pentylpyrrolidine-3-carboxylate Precursors of the Aza Analogues of (+)- and (−)-Methylenolactocin

Abstract

Enantiomerically pure methyl esters of (+)-(2R,3S)- and (−)-(2S,3R)-5-oxo-2-pentylpyrrolidine-3-carboxylic acid with 99% and 98% ee were obtained by enzymatic resolution of the corresponding racemic mixture using α-chymotrypsin and pig-liver acetone powder, respectively. Their absolute configurations were established by chemical methods, i.e., conversion of the trans-γ-lactam moiety to the corresponding γ-lactone of known configuration. The favorable interactions between the trans-γ-lactam and α-chymotrypsin were rationalized by molecular-mechanics calculations, which suggest a different situation for the cis-diastereoisomer.