Ketoreductase/Transaminase, One-Pot, Multikilogram Biocatalytic Cascade Reaction

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.

Automated summary

A biocatalytic cascade for producing tert-butyl ((2R,4R)-2-methyltetrahydro-2H-pyran-4-yl)carbamate 6 has been demonstrated at a multikilogram scale. The process involves resolving a racemic ketone by selectively reducing the undesired ketone and then catalyzing enantioselective transamination to form the desired amine. The product is recovered after Boc protection in the aqueous reaction.