Conversion of γ‐ and δ‐Keto Esters into Optically Active Lactams. Transaminases in Cascade Processes

E-ISSN： 1615-4169|360|4|686-695

ISSN： 1615-4150

Source： ADVANCED SYNTHESIS & CATALYSIS, Vol.360, Iss.4, 2018-02, pp. : 686-695

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Abstract

AbstractA one‐pot two‐step enzymatic strategy has been designed for the production of optically active γ‐ and δ‐lactams in aqueous medium under mild conditions. The approach is based on the biotransamination of ethyl or methyl keto esters bearing different alkyl or aryl substitution patterns at α‐position to the ketone functionality. In this manner, the keto esters were transformed into the corresponding amino esters with excellent conversions, which underwent spontaneous cyclisation in the reaction medium without addition of external reagents. Depending on the transaminase selectivity, both lactam enantiomers can be obtained, so initial enzyme screenings were performed using commercially available and made in house enzymes. Reaction conditions were optimised focusing on the substrate concentration, temperature and ratio of amine donor vs acceptor. Thus, ten γ‐ and δ‐lactams were obtained in good to high isolated yields (70–90%) and excellent selectivities (94–99%) after one or two days at 30 or 45 °C.