Candida viswanathii as a novel biocatalyst for stereoselective reduction of heteroaryl methyl ketones: a highly efficient enantioselective synthesis of (S)-α-(3-pyridyl)ethanol

Abstract

The enantioselective reduction of various heteroaryl methyl ketones, such as 2-, 3-, and 4-acetyl pyridines, 2-acetyl thiophene, 2-acetyl furan, and 2-acetyl pyrrole, was carried out with the resting cells of a novel yeast strain Candida viswanathii. Excellent results were obtained with acetyl pyridines. Moderate conversion took place with 2-acetyl thiophene, but no significant reduction was observed with 2-acetyl furan and 2-acetyl pyrrole. In the case of acetyl pyridines, the bioreduction was found to be sensitive toward the nature of substitution on the pyridine nucleus and the conversion followed the order 4-acetyl pyridine > 3-acetyl pyridine > 2-acetyl pyridine. Reduction of 3-acetyl pyridine with a high conversion (>98%) and excellent enantioselectivity (ee >99%) provided the biocatalytic preparation of (S)-α-(3-pyridyl)ethanol, a key intermediate of pharmacologically interesting alkaloids–akuamidine and heteroyohimidine. Finally, preparative scale reduction of 3-acetyl pyridine has been carried out with excellent yield (>85%) and almost absolute enantioselectivity (ee >99.9%).