Production of (R)-chiral alcohols by a hydrogen-transfer bioreduction with NADH-dependent Leifsonia alcohol dehydrogenase (LSADH)

Alcohol dehydrogenase (LSADH) isolated from Leifsonia sp. S749 was used to produce (R)-chiral alcohols. The enzyme with a broad substrate range reduced various prochiral ketones and keto esters to yield optically active secondary alcohols with a high enantiomeric excess. LSADH transferred the pro-S hydrogen of NADH to the carbonyl moiety of phenyl trifluoromethyl ketone 13 through its re face to give (S)-1-phenyl-2,2,2-trifluoroethanol 40. LSADH was able to efficiently reproduce NADH when 2-propanol was used as a hydrogen donor in the reaction mixture.

LSADH catalyzed the enantioselective reduction of more than 25 ketones with high conversion and enantiomeric purity to give (R)-form alcohols.Figure optionsDownload as PowerPoint slide

Ethyl (R)-2-hydroxy-3-methylbutanoateC7H14O3[α]D21=-10.5 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

Ethyl (S)-4-phenyl-2-hydroxybutanoateC12H16O3[α]D21=+14.3 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: S

Methyl (S)-4-bromo-3-hydroxybutanoateC5H9O3Br[α]D22=-25.9 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: S

(S)-1-Phenyl-2,2,2-trifluoroethanolC8H7OF3[α]D21=+23.5 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: S

(R)-1-(3-Chlorophenyl)ethanolC8H9OCl[α]D21=+42.7 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

(R)-1-(4-Chlorophenyl)ethanolC8H9OCl[α]D21=+53.9 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

(R)-1-(3-Bromophenyl)ethanolC8H9OBr[α]D21=+43.3 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

(R)-1-(4- Bromophenyl)ethanolC8H9OBr[α]D21=+41.8 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

(S)-2-Chloro-1-(3-chlorophenyl)C8H8OCl[α]D21=+46.8 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: S

(R)-1-(2,4-Dichlorophenyl)ethanolC8H8OCl[α]D21=+44.0 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

(R)-1-(3-Methoxyphenyl)ethanolC9H12O2[α]D22=+44.4 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

(R)-1-(3,4-Dimethoxyphenyl)propan-2-olC11H16O3[α]D22=-21.7 (c 0.4, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

(R)-1-Piperonyl-2-propanolC10H12O3[α]D23=-34.8 (c 0.4, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R

(S)-1-(3,4-Methylenedioxyphenyl)-2-chloroethanolC9H9O3Cl[α]D22=+45.6 (c 0.5, CH3Cl)Source of chirality: bioreductionAbsolute configuration: S

(R)-1-N-Boc-3-pyrrolidinolC9H17NO3[α]D23=-19.7 (c 0.3, CH3Cl)Source of chirality: bioreductionAbsolute configuration: R