Multienzymatic preparation of 3-[(1R)-1-hydroxyethyl]benzoic acid and (2S)-hydroxy(phenyl)ethanoic acid

The use of two oxidoreductases (an aldoketo reductase from Escherichia coli JM109 and an alcohol dehydrogenase from Lactobacillus brevis) has demonstrated that it is possible to prepare enatiomerically pure diols in a one-pot operation. The reactions were applied to the synthesis of (1R)-1-[3-(hydroxymethyl)phenyl]ethanol and (1S)-1-phenylethane-1,2-diol, using a two-step procedure. The yield is nearly quantitative and the enantiomeric purity is greater than 95%. A third step has been introduced by adding a cell biocatalyst showing dihydrodiol dehydrogenase activity from Pseudomonas fluorescens N3. This allows for the preparation of 3-[(1R)-1-hydroxyethyl]benzoic acid and (2S)-hydroxy(phenyl)ethanoic acid.

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3-[(1R)-Hydroxyethyl]benzaldehydeC9H10O2Ee = >95%[α]D25=+31.45 (c 0.46 mg, CHCl3)Source of chirality: bioconversionAbsolute configuration: (R)

(1S)-1-Phenylethane-1,2-diolC8H10O2Ee = >95%[α]D25=+68.2 (c 0.58 mg, CHCl3)Source of chirality: bioconversionAbsolute configuration: (S)

(2S)-Hydroxy(phenyl)ethanoic acidC8H8O3Ee = >95%[α]D25=+153.4 (c 0.88 mg, H2O)Source of chirality: bioconversionAbsolute configuration: (S)

(1R)-1-[3-(Hydroxymethyl)phenyl]ethanolC9H12O2Ee = >95%[α]D25=+37.5 (c 1.3 mg, CHCl3)Source of chirality: bioconversionAbsolute configuration: (R)

3-[(1R)-Hydroxyethyl]benzoic acidC9H10O3Ee = >95%[α]D25=+29.9 (c 1.55 mg, CHCl3)Source of chirality: bioconversionAbsolute configuration: (R)