Synthesis and biological properties of multivalent iminosugars

Abstract

Glycosidases are extremely widespread enzymes responsible for the cleavage of glycosidic bonds in glycoconjugates found in living organisms. Although it was well-known that the naturally occurring iminosugars are powerful glycosidase inhibitors, the development of inhibitors based on iminosugar clusters was not explored for a long period of time. However, over the past few years, several studies demonstrated that multivalent iminosugars can strongly inhibit the above-mentioned enzymes. In this review, we will focus on the different strategies developed to synthesize these multivalent architectures, from the total synthesis of divalent iminosugars to the preparation of complex systems bearing twenty-five iminosugar units. The enzyme inhibitory properties of the various multivalent iminosugars prepared to date will also be compared in order to infer the valence and the three-dimensional arrangement required for the most efficient inhibition activity.