Enzymatic Resolution of cis-Dimethyl 1-Acetylpiperidine-2,3-Dicarboxylate for Fine Chemicals Preparation

Abstract

Biocatalysis has become recently a promising tool for chemical synthesis. In particular, enzymes as lipases and esterases are often used to resolve racemicmixtureof esters.Weproposeaenantiospecific enzymatic resolution in order to produce enatiopure synthons precursor of pharmaceutical active substances. The process consists in the enantiospecific hydrolysis of a water-soluble racemic mixture of cis-dimethyl 1-acetylpiperidine2,3-dicarboxylate catalyzed by Candida antarctica lipase B. The separation of product in (2R,3S) configuration from unreacted substrate in (2S,3R) configuration is easily obtained by organic phase extraction. This latter form could be used as enantiomerically pure precursor in the (4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridine synthesis, an expensive building block of the antibiotic Moxifloxacin. By the other hand, the hydrolysed form with (2R,3S) configuration could be used for the preparation of neuromediator analogues. Studies concerning hydrolysis and use of immobilized enzyme has been carried out in order to evaluate its industrial application. The enzyme demonstrate high enantiospecificity, concerning the (2R,3S) enantiomer, and regioselectivity, concerning the ester in position 3. The process has been subject for patent application.