Beyond enzymatic promiscuity: asymmetric induction by l-proline on lipase catalyzed synthesis of polyfunctionalized 4H-pyrans

Abstract

We report herein the synthesis of polysubstituted 4H-pyrans catalysed by PPL via a three-component reaction of aldehyde, malononitrile and acetyl acetone. The catalytic activity of PPL with other lipases and its reactivity profile in different reaction media were thoroughly studied. Although the change in enzyme reaction specificity induced by metal substitutions and amino acids is well known, non-covalent introduction of an amino acid into an enzymatic promiscuous reaction to achieve stereoselectivity through co-operative catalysis has not been explored yet. In an interesting observation, we have noted that addition of L-proline to PPL catalysed reactions can induce stereoselectivity in the formation of polysubstituted 4H-pyrans while such MCRs catalyzed by PPL alone give only racemic products.