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.