Chemoenzymatic Sequential Multistep One-Pot Reaction for the Synthesis of (1S,2R)‑1-(Methoxycarbonyl)cyclohex-4-ene-2-carboxylic Acid with Recombinant Pig Liver Esterase

• Published in: Organic process research & development 2015-12, Vol.19 (12), p.2034-2038
• Main Authors: Süss, Philipp, Borchert, Sonja, Hinze, Janine, Illner, Sabine, von Langermann, Jan, Kragl, Udo, Bornscheuer, Uwe T, Wardenga, Rainer
• Format: Article
• Language: English
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/acs.oprd.5b00294

In this work, the development of a chemoenzymatic process for the production of (1S,2R)-1-(methoxycarbonyl)cyclohex-4-ene-2-carboxylic acid by ECS-PLE06 (recombinant pig liver esterase) is presented. Herein an optimized esterification protocol, starting from the economically favored meso-anhydride 1b, was established and combined with the highly selective ECS-PLE06-catalyzed desymmetrization reaction. Both reactions proceed under mild reaction conditions, and the excellent selectivity of ECS-PLE06 results in an enantiomeric excess of ≥99.5% ee. Furthermore, the presented one-pot synthesis facilitates higher isolated yields of up to 84% in comparison to the classical two-step synthesis route (70% isolated yield), which requires more expensive starting materials and two separate workup steps.