Preparation of water-soluble glycopolymers derived from five-membered iminosugars

Abstract

Iminosugars are carbohydrate mimetics that constitute the main group of oligosaccharide processing enzyme inhibitors. They play an important role in cell-cell recognition processes, thereby presenting a wide range of potential therapeutic applications. In this work, we present the first examples of glycopolymers containing five-membered iminosugars. The preparation is carried out by constructing first a biocompatible water-soluble and pH-responsive 2-hydroxyethyl methacrylate (HEMA)-based copolymer by RAFT polymerization with an excellent control on the copolymer composition and low polydispersity (Mn = 19,800; Mw = 23,800; Mw/ Mn = 1.2; experimental copolymer mole composition (by 1 H NMR): pHEMA49%-co-pDMAEMA51%). One-pot azidation of its primary hydroxyl groups by Mitsunobu reaction led to a full functionalization of the HEMA residues. Subsequently, a selection of alkynyl pyrrolidine iminosugars showing glycosidase inhibition properties, were anchored to the functionalized azido-polymer through CuAAC click reaction furnishing successfully the aimed water-soluble glycopolymers, which were then subjected to biological evaluation as enzyme inhibitors.