Efficient synthesis of 5'-O-laurate of 1-beta-D-arabinofuranosylcytosine via highly regioselective enzymatic acylation in binary solvent mixtures.

Regioselective enzymatic acylations of 1-beta-D-arabinofuranosylcytosine (ara-C) with vinyl laurate (VL) in binary organic solvents were explored for the preparation of 5'-O-laurate of ara-C. Among the nine kinds of enzymes, Novozym 435 showed the highest regioselectivity (>99.9%) towards the 5'-OH of ara-C. This lipase showed higher catalytic activity in hexane-pyridine than in other tested solvent mixtures. The most suitable VL to ara-C molar ratio, initial water activity, and reaction temperature were shown to be 15:1, 0.07, and 50 degrees C, respectively, under which the initial reaction rate and the maximum substrate conversion were as high as 84.0 mmol L(-1) h(-1) and 98.1%, respectively. The product of Novozym 435-catalyzed acylation was characterized by (13)C NMR and confirmed to be 5'-O-laurate of ara-C. 2010 Elsevier Ltd. All rights reserved.