Facile Stereoselective Reduction of Prochiral Ketones by using an F420-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 F-420-dependent alcohol dehydrogenase (ADF) fromMethanoculleus thermophilicusthat 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 F(420)or the unnatural cofactor FOP to achieve full conversion. This study reveals that deazaflavoenzymes complement the biocatalytic toolbox for enantioselective ketone reductions.

Automated summary

This study demonstrates that a previously unexplored class of enzymes can effectively reduce various ketones to enantiopure alcohols, offering a new approach for the synthesis of optically pure alcohols.