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Identification and Implementation of Biocatalytic Transformations in Route Discovery: Synthesis of Chiral 1, 3-Substituted Cyclohexanone Building Blocks

Organic Process Research & Development. 2018; 
Timin Hadi, Alba Diaz-Rodriguez, Diluar Khan, James P Morrison, Justin M Kaplan, Kathleen T Gallagher, Markus Schober, Michael R Webb, Kristin Brown, Douglas Fuerst, Radka Snajdrova, and Gheorghe-Doru Roiban
Products/Services Used Details Operation
Codon Optimization The genes encoding EREDs and nitrilases were codon optimised for expression in E. coli BL21(DE3), synthesised, and cloned into pET28a at GenScript. Transformation, shake flask enzyme expression and 50 L fermentation trials were performed as described previously Get A Quote

摘要

Several biocatalytic approaches for the preparation of optically pure methyl 3 oxocyclohexanecarboxylates (S)-, (R)-1 and 3-oxocyclohexanecarbonitriles (S)-, (R)-2 have been successfully demonstrated. Screening of reaction-focused enzyme collections was used to identify initial hits using three enzymatic strategies. Reaction optimization and scale-up enabled the production of chiral intermediates for route scouting efforts on scales of up to 100 g. The enzymes applied in these processes (lipases, enoate reductases and nitrilases) have been shown to be robust catalysts for drug manufacturing and represent a green alternative to conventional methods to access these chiral cyclohexanone building blocks.

关键词

Biocatalysis, Enoate Reductases, Nitrilases, Lipases, Active Pharmaceutical Ingredients.