Asymmetric reduction of ketones by employing Rhodotorula sp. AS2.2241 and synthesis of the β-blocker (R)-nifenalol

A broad range of prochiral ketones were efficiently reduced to the corresponding optically active secondary alcohols using resting cells of Rhodotorula sp. AS2.2241. The microbial reduction system exhibited high activity and enantioselectivity in the reduction of various aromatic ketones and acetylpyridines (>97% ee), but moderate to high enantioselectivity in the reduction of α- and β-keto esters. (R)-Nifenalol, a β-adrenergic blocker, was also synthesized using 2-bromo-1(R)-(4-nitrophenyl)ethanol (97% ee) which was prepared through the asymmetric reduction of 2-bromo-1-(4-nitrophenyl)ethanone employing Rhodotorula sp. AS2.2241. The simple preparation and the high activity of the biocatalyst turned this system into a versatile tool for organic synthesis.

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(S)-(−)-1-PhenylethanolC8H10OEe = 99%[α]D = −59.2 (c 0.658, CHCl3)Absolute configuration: (S)

(S)-(−)-1-(4-Nitrophenyl)ethanolC8H9NO3Ee = >99%[α]D = −30.5 (c 1.083, EtOH)Absolute configuration: (S)

(S)-(−)-1-(4-Bromophenyl)ethanolC8H9BrOEe = >99%[α]D = −36.0 (c 0.775, CHCl3)Absolute configuration: (S)

(S)-(−)-1-(4-Chlorophenyl)ethanolC8H9ClOEe = >99%[α]D = −47.8 (c 0.758, Et2O)Absolute configuration: (S)

(S)-(−)-1-(4-Methoxyphenyl)ethanolC9H12O2Ee = >99%[α]D = −56.4 (c 0.442, CHCl3)Absolute configuration: (S)

(R)-(−)-2-Bromo-1-phenylethanolC8H9BrOEe = >99%[α]D = −39.5 (c 0.592, CHCl3)Absolute configuration: (R)

(R)-(−)-2-Chloro-1-phenylethanolC8H9ClOEe = >99%[α]D = −50.7 (c 0.225, cyclohexane)Absolute configuration: (R)

(S)-(−)-Phenyl-1-propanolC9H12OEe = >99%[α]D = −50.8 (c 1.03, CHCl3)Absolute configuration: (S)

(R)-(−)-2-Bromo-1-(4-nitrophenyl)ethanolC8H8BrNO3Ee = 97%[α]D = −35.4 (c 0.942, CHCl3)Absolute configuration: (R)

(R)-(−)-2-Isopropylamino-1-(4-nitrophenyl)ethanolC11H16N2O3Ee = 97%[α]D = −41.5 (c 0.286, H2O)Absolute configuration: (R)

(S)-(−)-2-Pyridyl-1-ethanolC7H9NOEe = >99%[α]D = −25.0 (c 1.39, CHCl3)Absolute configuration: (S)

(S)-(−)-3-Pyridyl-1-ethanolC7H9NOEe = 99%[α]D = −47.0 (c 0.625, MeOH)Absolute configuration: (S)

(S)-(−)-4-Pyridyl-1-ethanolC7H9NOEe = 97%[α]D = −44.0 (c 1.03, MeOH)Absolute configuration: (S)

(R)-(−)-Methyl mandelateC9H10O3Ee = 86%[α]D = −124.8 (c 0.8, MeOH)Absolute configuration: (R)

(S)-(−)-3-Hydroxy-3-phenylpropionic acid ethylesterC11H14O3Ee = >99%[α]D = −52.7 (c 1.0, CHCl3)Absolute configuration: (S)

(S)-(+)-Ethyl 3-hydroxybutyrateC6H12O3Ee = 74%[α]D = +22.2 (c 0.442, CHCl3)Absolute configuration: (S)

(S)-(−)-Ethyl 4-chloro-3-hydroxybutanoateC6H11ClO3Ee = 64%[α]D = −11.4 (c 1.59, CHCl3)Absolute configuration: (S)