Enzymatic resolution and cholinergic properties of (±)3-quinuclidinol derivatives

Abstract

Resolution of (±)3-quinuclidinol into its enantiomers was obtained, at relatively high yield, based on the stereoselective enzymatic hydrolysis of R-(−)-3-quinuclidinyl butyrate by horse serum butyrylcholinesterase. The S-(+) isomer of 3-quinuclidinol was obtained from the racemate of 3-quinuclidinyl butyrate by a complete digestion of the (−) ester; the R-(−) isomer of 3-quinuclidinol was prepared by a partial hydrolysis of the racemate. The enantiomers obtained by this method were of high optical purity ([ α] D 25 = (+)46°). The cholinergic interactions of the benzilate esters of the 3-quinuclidinol enantiomers were characterized in mice in vivo and in isolated guinea pig ileum. The R to S potency ratio is around 10–15 for the muscarinic antagonist 3-quinuclidinyl benzilate (QNB) in the in vivo experiments compared to the reported ratio of 100 in competition experiments in vitro .