Resolution of N-hydroxymethyl vince lactam catalyzed by lipase in organic solvent

BACKGROUND: The enantiomers of N-hydroxymethyl vince lactam are important intermediates during the synthesis of chiral drugs. The preparation of its single enantiomer can be performed through enzymatic resolution. The aim of this work is to obtain (1S, 4R)-N-hydroxymethyl vince lactam with high enantiomeric purity via lipase-catalyzed enantioselective transesterification in organic solvents. To achieve this, effects of various reaction conditions (including lipase sources, acyl donor, substrate molar ratio, organic solvent, temperature, and water activity) on the enzyme activity as well as enantioselectivity were investigated. RESULTS: The results of the study showed that the enantiopreference for all the selected enzymes was (4S, 1R)-N-hydroxymethyl vince lactam in enantioselective transesterification of racemic N-hydroxymethyl vince lactam. Under the selected optimum conditions, the highest enantioselectivity (E = 33.8) was obtained with a higher enzyme activity (20.3 mu mol g1 min1) for Mucor miehei lipase (MML) when vinyl valerate was used as the acyl donor. Besides, the remained (1S, 4R)-N-hydroxymethyl vince lactam with high enantiomeric purity (ee > 99%) was obtained when the conversion was about 60%. CONCLUSION: The results obtained clearly demonstrated potential for industrial application of lipase in resolution of N-hydroxymethyl vince lactam through enantioselective transesterification. (c) 2012 Society of Chemical Industry