Convenient Polymer-Supported Synthetic Route to Heterobifunctional Polyethylene Glycols

Abstract

Conventional synthesis of heterobifunctional poly(ethylene glycol) derivatives, especially of medium size, is a rather tedious task. A straightforward solid-phase methodology has been developed that is illustrated here by the synthesis of α-pyridyldithio-ω-hydroxy-poly(ethylene glycol)₆₀₀. This derivative was prepared from resin-bound PEG₆₀₀ with a global yield of 65% for 6 individual steps, i.e., with an average yield of 93%/step. Intermediate purification steps simply consisted of resin washing. Progress of each reaction toward completion could conveniently be monitored by ¹³C NMR of the resin-bound PEG derivatives. This example highlights both the versatility and efficiency of combining polymer-supported synthesis with direct ¹³C-NMR characterization of the intermediate compounds.