Controllable selective synthesis of a polymerizable prodrug of cytarabine by enzymatic and chemical methods

Selectivity of enzymatic and chemical methods for transesterifications of cytarabine with divinyl dicarboxylates was described. Catalysis by lipase acrylic resin from Candida antarctica (CAL-B) in acetone facilitated the single step synthesis of polymerizable 5 '-O-acyl cytarabine derivatives in high yields, while the use of alkaline protease from Bacillus subtilis (subtilisin) in pyridine afforded the mixture products of 5 '-O-acyl and 4-N-acyl cytarabine derivatives. Interestingly, polymerizable 4-N-acyl cytarabine vinyl derivatives can be selectively prepared by chemical transesterification in dioxane. The obtained series of cytarabine derivatives would be useful for a significant monomer for a polymeric anticancer drug. (c) 2005 Elsevier Ltd. All rights reserved.