Enzymatic synthesis of unique thymidine-containing polyphenols

A two-enzyme reaction sequence was utilized to generate phenolic polymers containing a thymidine pendent group. Thymidine was used as the model nucleoside and a trifluoroethyl ester derivative of p-hydroxyphenylacetic acid was used as the phenolic derivative. Regioselective acylation of thymidine at the 5′-hydroxyl was achieved in nearly anhydrous CH₃CN using the lipase from Candida antarctica. This was followed by the polymerization of the phenolic nucleoside derivative catalyzed by the peroxidase from soybean hulls. A potential advantage of the coupled enzymatic approach is the high degree of control that can be exerted over both reactions that comprise the synthetic scheme for the generation of thymidine-containing polyphenols.