Ketoreductase/Transaminase, One-Pot, Multikilogram Biocatalytic Cascade Reaction
Michael P. Burns, Wenying Bi, Hui Kim, Manjinder S. Lall, Chao Li, Brian T. O’Neill
Abstract
A biocatalytic cascade to produce tert-butyl ((2R,4R)-2-methyltetrahydro-2H-pyran-4-yl)carbamate 6 has been demonstrated at the multikilogram scale. In this reaction, a racemic ketone is resolved by reducing the undesired ketone using a ketone reductase (KRED). The reduction is stereospecific for the 2-position of substrate (2S)-ketone leaving the (2R)-ketone unreacted. After the (2S)-ketone has been depleted, a transaminase is added to catalyze the enantioselective transamination of the ketone, resulting in formation of the (2R, 4R)-amine 6. The product is recovered from the aqueous reaction after Boc protection.
Topics & Concepts
KetoneChemistryStereospecificityTransaminationAmine gas treatingCascade reactionBiocatalysisTransaminaseOrganic chemistryEnantioselective synthesisSubstrate (aquarium)CatalysisReaction mechanismEnzymeOceanographyGeologyEnzyme Catalysis and ImmobilizationMicrobial Metabolic Engineering and BioproductionCarbohydrate Chemistry and Synthesis