Novozym 435-catalyzed regioselective acylation of 1-β-d-arabinofuranosylcytosine in a co-solvent mixture of pyridine and isopropyl ether

Novozym 435-catalyzed regioselective acylation of 1-β-d-arabinofuranosylcytosine (ara-C) for the preparation of its 5′-O-acyl derivative has been successfully performed for the first time. The reaction was dramatically accelerated by using vinyl acetate as the acyl donor and the co-solvent mixture of pyridine and isopropyl ether (3/1, v/v) as the reaction medium. Comparative study showed a lower Ea for the reaction taking place in the co-solvent mixture of pyridine and isopropyl ether (3/1, v/v) than in other media tested. The most suitable initial water activity, 1-β-d-arabinofuranosylcytosine concentration, molar ratio of vinyl acetate to 1-β-d-arabinofuranosylcytosine and reaction temperature were 0.11, 40 mM, 15:1 and 50 °C, respectively, under which the substrate conversion and the regioselectivity were as high as >97 and >99%, respectively, after a reaction time of 12 h.