Enoate reductases belonging to the Old Yellow Enzyme (OYE) family were employed to develop a biocatalysed approach to methyl (S)-2-bromobutanoate, a key intermediate for the introduction of a particular stereogenic unit into the molecular skeleton of a certain class of chiral drugs. Methyl (Z)-2-bromocrotonate afforded, respectively, (S)-2-bromobutanoic acid (ee = 97%) and methyl (S)-2-bromobutanoate (ee = 97%) by baker's yeast fermentation and by OYE1À3 biotransformations. The bioreductions of other methyl 2-haloalkenoates were also considered. It was observed that the (Z)-and (E)-diastereoisomers of Rbromo unsaturated esters afforded the same enantiomer of the corresponding reduced product.

No abstract

The ene-reductase-mediated reduction of the carbon-carbon double bond of some alkyl 2substituted butenedioates was investigated. The stereochemical outcome of the reaction was found to be influenced by steric effects. Ethyl and butyl citraconates were converted into the corresponding alkyl (R)-2-methylsuccinates with excellent enantioselectivity, whereas ethyl and butyl mesaconates were completely unreactive. Methyl 2-substituted fumarates were reduced to enantiomerically enriched methyl (S)-2-substituted succinates, whereas the (Z)-stereoisomers were left unreacted by enereductases. Labelling experiments were performed to investigate the mechanism of these bioreductions and explain their stereochemical outcome.

The enantioselective biocatalyzed reduction of the C=C bond of some (Z)‐methyl α‐halo‐β‐arylacrylates was investigated. The reaction was performed by baker's yeast fermentation and Old Yellow Enzymes 1–3 mediated biotransformations. The final products were, respectively, enantiomerically enriched (S)‐α‐halo‐β‐arylpropionic acids and their methyl esters, and ester hydrolysis was promoted in the whole cell system. High conversions and enantioselectivity values were observed when the aromatic ring was substituted by an electron‐withdrawing group. Further manipulation of two of these enantiomerically enriched (S)‐haloacids afforded p‐substituted D‐phenylalanines.

No abstract