PREPARATION OF CHIRAL CYANOHYDRINS BY AN OXYNITRILASE-MEDIATED TRANSCYANATION

The transcyanation of aromatic and aliphatic aldehydes 1 (RCHO) with acetone cyanohydrin is catalyzed by the enzyme D-oxynitrilase to afford (R)-cyanohydrins 2 (RCH(OH)CN). The biocatalytic method using acetone cyanohydrin gives products of high enantiomeric purity with better consistency than similar conditions using hydrogen cyanide as the cyanide source. The use of an ether-buffer biphasic solvent system is essential for producing products of optimum optical purity, but the solubility properties of the substrate have a pronounced effect on the enantiomeric purity of the final product. A discussion relating the solubility partition coefficient (log P) of a substrate to the enantiomeric purity of the product as a guide for predicting the outcome with new substrates is presented. Application of the method to the preparation of the following cyanohydrins is reported (R, ee): a, C6H5, 92% ee; b, 3,4-(CH2O2)C6H3, 90% ee; c, 2-(CH3O)C6H4, 96% ee; d, C6H5CH2, 88% ee; e, CH3SCH2CH2, 92% ee; f, CH3(CH2)5CH2, 92% ee; g, (CH3)3C, 92% ee; h, c-C6H11, 96% ee; i, CH3O2C(CH2)6CH2, 97% ee; j, (E,E)-CH3CH = CHCH = CH, 96% ee; k, (CH3)2C = CHCH2CH2C(CH3) = CH, 99% ee.