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

• Published in: ChemistrySelect
• Main Authors: Fogal S., Bergantino E., Motterle R.
• Other Authors: Fogal, S., Bergantino, E., Motterle, R.
• Format: Article in Journal/Newspaper
• Language: English
• Published: John Wiley and Sons Inc 2022
• Subjects: Antarc*; Antarctica
• Online Access: http://hdl.handle.net/11577/3444199; https://doi.org/10.1002/slct.202104090

This work presents the enantioselective resolution of a water-soluble 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-1H-pyrrolo[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.