화학공학소재연구정보센터
Enzyme and Microbial Technology, Vol.42, No.5, 414-420, 2008
Two-step synthesis of structure-diverse D-galactose conjugates and polymeric prodrugs of floxuridine via controllable regioselective enzymatic acylation of 3'- or 5'-OH group of floxuridine
We achieved an effective way of controllable regioselective acylation of primary or secondary hydroxyl group of floxuridine with different enzymes. Polymerizable 5'-O-acyl-floxuridine derivatives were synthesized by CAL-B (immobilized lipase from Candida antarctica) in acetonitrile or subtilisin in pyridine, and the 3'-O-acyl-floxuridine derivatives by PSL-C (Pseudomonas cepacia, immobilized) in THF with high selectivity and yields. These resulting monomers were subjected to the further transformations in the second step, i.e. chemo-polymerization in DMF initiated by azobisisobutyronitrile to give polymeric prodrugs with the same backbone and different branch position, and enzymatic conjugation Of D-galactose for the synthesis of D-galactose-floxuridine conjugates with acylation position-diversity, which were potential targeting drugs. (C) 2007 Elsevier Inc. All rights reserved.