Synthesis of optically active α-bromohydrins via reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase

Enantiomerically pure (S)-α-bromohydrins were prepared by the reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase from Candida magnolia with high yield and excellent enantiomeric excess when methyl tert-butyl ether was employed as the co-solvent, while avoiding the formation of by-products. This provides a new approach to access these chiral α-bromohydrins which are of pharmaceutical importance.

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(S)-2-Bromo-1-phenylethanolC8H9BrOee: >99%[α]D20=+13.1 (c 0.62, methanol).Source of chirality: Enzymatic reductionAbsolute configuration: (S)

(S)-2-Bromo-1-(4-methylphenyl)ethanolC9H11BrOee: >99%[α]D20=+20.0 (c 1.92, methanol).Source of chirality: Enzymatic reductionAbsolute configuration: (S)

(S)-2-Bromo-1-(3-methoxyphenyl)ethanolC9H11BrO2ee: >99%[α]D20=+19.7 (c 2.0, methanol)Source of chirality: Enzymatic reductionAbsolute configuration: (S)

(S)-2-Bromo-1-(4-methoxyphenyl)ethanolC9H11BrO2ee: >99%[α]D20=+29.0 (c 1.88, methanol).Source of chirality: Enzymatic reductionAbsolute configuration: (S)

(S)-2-Bromo-1-(3-nitrophenyl)ethanolC8H8BrNO3ee: >99%[α]D20=+18.5 (c 1.36, methanol).Source of chirality: Enzymatic reductionAbsolute configuration: (S)

(S)-2-Bromo-1-(4-nitrophenyl)ethanolC8H8BrNO3ee: >99%[α]D20=+20.4 (c 1.6, methanol).Source of chirality: Enzymatic reductionAbsolute configuration: (S)

(S)-2-Bromo-1-(4-chlorophenyl)ethanolC8H8BrClOee: >99%[α]D20=+21.9 (c 1.28, methanol).Source of chirality: Enzymatic reductionAbsolute configuration: (S)

(S)-2-Bromo-1-(3,4-dichlorophenyl)ethanolC8H7BrCl2Oee: >99%[α]D20=+16.1 (c 0.82, methanol).Source of chirality: Enzymatic reductionAbsolute configuration: (S)

(S)-2-Bromo-1-(4-flurophenyl)ethanolC8H8BrFOee: >99%[α]D20=+16.1 (c 1.4, methanol).Source of chirality: Enzymatic reductionAbsolute configuration: (S)