Novel route for the resolution of both enantiomers of dropropizine by using oxime esters and supported lipases of Pseudomonas cepacia

Resolution of (R)- and (S)-dropropizine which is an antitussive and central sedative therapeutic agent in high optical and chemical yields was achieved by lipases of Pseudomonas cepacia supported on ceramic particles (lipase PS-C) and on diatomite (lipase PS-D) with oxime esters in organic solvents. The influence of several factors (lipase source, structural variations in oxime esters, the amount of lipase and its recyclability) on the enantioselectivity have been investigated. Different properties were used to describe the solvents, namely the hydrophobicity (quantified by log P) and the dielectic constant (epsilon). This enzymatic acylation using oxime esters was significant as only (S)-dropropizine and (R)-dropropizine monoacetate was obtained. (R)-Dropropizine monoacetate was chemically hydrolyzed to obtain (R)-dropropizine. The highest enantioselectivity was observed when O-acetyl benzophenone oxime was used. This enzymatic resolution provides a versatile method for getting the pure enantiomers of dropropizine by effectively optimizing the various reaction parameters. (C) 2001 Elsevier Science Inc. All rights reserved.