Versatile and Selective Synthesis of Click Chemistry Compatible Heterobifunctional Poly(ethylene glycol)s Possessing Azide and Alkyne Functionalities

Versatile route for click chemistry compatible heterobifunctional PEGS was established through preparation of alpha-tetrahydropyranyloxy-omega-hydroxyl poly(ethylene glycol) (THP-PEG-OH) via ring-opening polymerization of ethylene oxide using 2-(tetrahydro-2H-pyran-2-yloxy)ethanol as an initiator, followed by the functionalization of omega-OH group to either the azido or alkyne group. Quantitative azidation of THP-PEG-OH was confirmed froth the analysis of molecular functionality of the derivatives. While the conversion efficiency of omega-alkynation was appropriately 70%, the unreacted THP-PEG-OH fraction was successfully removed by ion-exchange chromatography after the carboxylation of the hydroxyl group with succinic anhydride. Then, the protecting group of the alpha-end, THP, was removed in mild acidic media, followed by two- or three-step modification of the resulting alpha-hydroxyl group to primary amino or thiol groups. Consequently, click chemistry compatible heterobifunctional PEG derivatives (X-PEG-Y; X = NH2 and SH, Y =Azide and Alkyne) were synthesized with high efficiency and controlled molecular weight.