Facile Stereoselective Reduction of Prochiral Ketones by using an F 420-dependent alcohol dehydrogenase

Effective procedures for the synthesis of optically pure alcohols are highly valuable. A commonly employed method involves the biocatalytic reduction of prochiral ketones. This is typically achieved by using nicotinamide cofactor‐dependent reductases. In this work, we demonstrate that a rather unexplored class of enzymes can also be used for this. We used an F420‐dependent alcohol dehydrogenase (ADF) from Methanoculleus thermophilicus that was found to reduce various ketones to enantiopure alcohols. The respective (S) alcohols were obtained in excellent enantiopurity (>99 % ee). Furthermore, we discovered that the deazaflavoenzyme can be used as a self‐sufficient system by merely using a sacrificial cosubstrate (isopropanol) and a catalytic amount of cofactor F420 or the unnatural cofactor FOP to achieve full conversion. This study reveals that deazaflavoenzymes complement the biocatalytic toolbox for enantioselective ketone reductions.
An alternative to NADH dependence: An F420‐dependent alcohol dehydrogenase can be used to asymmetrically reduce prochiral ketones. Conveniently, using a cheap sacrificial cosubstrate (isopropanol), the same enzyme can regenerate the deazaflavin cofactor.