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

• Published in: ChemistrySelect
• Main Authors: Fogal, Stefano, Bergantino, Elisabetta, Motterle, Riccardo
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2022
• Subjects: Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/slct.202104090; https://onlinelibrary.wiley.com/doi/pdf/10.1002/slct.202104090; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/slct.202104090

Abstract 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 (2 R ,3 S ) configuration from non‐reacted substrate in the (2 S ,3 R ) 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 (2 R ,3 S ) configuration can be used for the preparation of a neuromediator analogue. The lipase demonstrated enantioselectivity towards the (2 R ,3 S ) 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.