Chromatography-free synthesis of monodisperse oligo(ethylene glycol) mono-p-toluenesulfonates and quantitative analysis of oligomer purity

Abstract

Poly(ethylene glycol) (PEG) is a common building block for complex functional molecules. Because of its chain flexibility and hydrophilicity, it is widely used in bioconjugation chemistry. Modern applications require PEGs of high purity, hence well-defined, monodisperse PEG oligomers are gaining more attention. Here we report a large-scale synthetic procedure for monodisperse oligo(ethylene glycol) mono-p-toluenesulfonates, convenient intermediates of various heterobifunctional PEG derivatives. This method features no chromatographic purification, low total material cost and high purity of the products. In addition, oligomer dispersity of the products is determined quantitatively using reverse-phase HPLC and a number of bioconjugation-related functionalized PEG derivatives are prepared from the synthesized toluenesulfonates.