Mm. Salunkhe et Rv. Nair, Novel route for the resolution of both enantiomers of dropropizine by using oxime esters and supported lipases of Pseudomonas cepacia, ENZYME MICR, 28(4-5), 2001, pp. 333-338
Resolution of (R)- and (S)-dropropizine which is an antitussive and central
sedative therapeutic agent in high optical and chemical yields was achieve
d 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 enantiosel
ectivity have been investigated. Different properties were used to describe
the solvents, namely the hydrophobicity (quantified by log P) and the diel
ectic constant (epsilon). This enzymatic acylation using oxime esters was s
ignificant as only (S)-dropropizine and (R)-dropropizine monoacetate was ob
tained. (R)-Dropropizine monoacetate was chemically hydrolyzed to obtain (R
)-dropropizine. The highest enantioselectivity was observed when O-acetyl b
enzophenone oxime was used. This enzymatic resolution provides a versatile
method for getting the pure enantiomers of dropropizine by effectively opti
mizing the various reaction parameters. (C) 2001 Elsevier Science Inc. All
rights reserved.