Protease-mediated preparation of valganciclovir intermediate

Abstract An efficient and promising enzymatic process towards the synthesis of Valganciclovir intermediate, 2[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydropropyl-N-[(benzyloxy)carbonyl]- l -valinate has been developed. Protex 6L, a bacterial alkaline protease derived from a selected strain of Bacillus licheniformis and Alcalase 2.4L, a subtilisin protease has been found as a excellent biocatalyst towards the desymmetrization of 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]-1,3-propanediyl bis( l -valinate), an intermediate of Valgancyclovir hydrochloride. The access to mono-ester synthesis of high purity has been possible by hydrolysis reaction where the reaction parameters have been optimized in terms of various hydrolases, source and amount of Protex-6L, temperature, solvent and reaction time.