ENZYME-CATALYZED ORGANIC SYNTHESIS: REGENERATION OF DEUTERATED NICOTINAMIDE COFACTORS FOR USE IN LARGE-SCALE ENZYMATIC SYSNTHESIS OF DEUTERATED SUBSTANCES.

Article abstract of DOI:10.1021/ja00353a026

Procedures were developed for in situ regeneration of deuterated nicotinamide cofactors based on ethanol-1,1,-d//2/alcohol dehydrogenase/aldehyde dehydrogenase, deuterioformate (DCO//2** minus )/formate dehydrogenase, and glycolaldehyde-1,2,2-d//3/aldehyde dehydrogenase. These procedures can be used in the enzyme-catalyzed synthesis of deuterated organic products; representative procedures are illustrated by syntheses of (R)-trifluoroethanol-1-d//1 and L-glutamic alpha -d//1 acid on 0. 1 mol scales. For most synthetic applications, the first of these procedures (CH//3CD//2OH/ADH/AldDH) seems to provide the most practical method for in situ regeneration of deuterated nicotinamide cofactors. The high turnover numbers observed for the nicotinamide cofactors in these syntheses make possible the preparation of deuterated chiral substances with high isotopic purity, regardless of the stereochemistry of the hydride transfers to and from the nicotinamide cofactors.