Enzymatic Resolution of cis-Dimethyl-1-acetylpiperidine-2,3-dicarboxylate for the Preparation of a Moxifloxacin Building Block

摘要

This work presents the enantioselective resolution of a watersoluble racemic mixture of cis-dimethyl 1-acetylpiperidine-2,3-dicarboxylate catalyzed by Candida antarctica lipase B.The separation of the carboxylic acid product in its(2R,3S)configuration from non-reacted substrate in the(2S,3R)configuration was easily obtained by organic phase extraction.The latter molecule can be used as an enantiomerically pure precursor in the synthesis of(4aS,7aS)-octahydro-1Hpyrrolo[ 3,4-b]pyridine,an expensive building block in the production of the antibiotic Moxifloxacin.On the other hand,the hydrolyzed product in the(2R,3S)configuration can be used for the preparation of a neuromediator analogue.The lipase demonstrated enantioselectivity towards the(2R,3S)substrate enantiomer and regioselectivity towards the ester in position 3 of the molecule.Studies of hydrolysis kinetics and the use of the immobilized enzyme were performed to evaluate its industrial application.