Enzymatic enantioselective desymmetrization

4 steps to a robust and simple process suitable for industry

19-May-2017 - Germany

Enzymicals is focused on the development and piloting of chemo-enzymatic processes for the production of fine- and special chemicals. As an example Enzymicals presents a competitive process for production of optical pure (1S,2R)-1-Methyl cis-1,2,3,6-tetrahydrophthalate. This molecule is a major synthon as intermediate for the synthesis of many biologically active products, e.g. (+)-Aucantene, Anticapsin or Simeprevir.

The new process is the result of the collaboration between Enzymicals AG and Institute of Chemistry at the University of Rostock, department Analytics and Technical Chemistry, in the Central Innovation Program SME of the Federal Ministry for Economic Affairs and Energy funded project "Production of Fine Chemicals with Recombinant Pig Liver Esterases". The result is a sequential multistep one-pot-reaction by using recombinant pig liver esterase isoenzyme from Enzymicals enzyme panel.

Several steps were taken to optimize the process. The goal was to maximize yield, minimize material costs, improve reaction modes and intensify the whole process. The first part of optimization led to an acceptable yield with a very good enantomeric excess. By using readily available educts the synthesis costs could been cut significantly. As a one-pot reaction the downstream processing was simplified, atom economy was improved and a higher yield of the target substance was achieved. Finally the conversion from batch- to flow-process intensified the production.

The new developed chemo-enzymatic process is robust, simple and continuous. The target substance made by Enzymicals offers a purity of >98 % and an ee >99.5 %, which is a higher quality than available to date.

Original publication

Philipp Süss, Sabine Illner, Jan von Langermann, Sonja Borchert, Uwe T. Bornscheuer, Rainer Wardenga, and Udo Kragl; "Scale-Up of a Recombinant Pig Liver Esterase-Catalyzed Desymmetrization of Dimethyl Cyclohex-4-ene-cis-1,2-dicarboxylate"; Organic Process Research & Development; 2014

Philipp Süss, Sonja Borchert, Janine Hinze, Sabine Illner, Jan von Langermann, Udo Kragl, Uwe T. Bornscheuer, and Rainer Wardenga; "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"; Organic Process Research & Development; 2015

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