Enantioselective dehydrogenation of β-hydroxysilanes by horse liver alcohol dehydrogenase with a novel in-situ NAD+ regeneration system

Abstract

Dehydrogenation of 2-trimethylsilyl-1-propanol (1) was carried out with horse liver alcohol dehydrogenase (HLADH, EC 1.1.1.1). It was found that the hydrogenation of 1 proceeded enantioselectively with only HLADH and a catalytic amount of NAD+ due to in-situ NAD+ regeneration based on a specific property of β-carbonylsilanes. That is, (+)-1 was enantioselectively dehydrogenated by HLADH to 2-trimethylsilyl-1-propanal, which was spontaneously degraded by addition of water into trimethylsilanol and n-propanal. Then, NAD+ was regenerated through HLADH-catalyzed reduction of n-propanal to n-propanol. On the other hand, dehydrogenation of the carbon analogue of 1 was negligible with a catalytic amount of NAD+, indicating that the in-situ NAD+ regeneration was not available without the specific property of organosilicon compounds. Other primary β-hydroxysilanes having different substituents on the chiral center or on the silicon atom were also found to serve as substrates in enantioselective dehydrogenation by HLADH with this novel NAD+ regeneration system. Chiral recognition of HLADH toward primary alcohols is also discussed.