Gem-diamine 1-N-iminosugars as new versatile glycomimetics: synthesis, biological and pharmacological activity, and therapeutic potential

Abstract

Iminosugars, carbohydrate analogues that have a nitrogen atom in place of the carbohydrate ring oxygen atom, have attracted increasing interest as new glycomimetics. Gem-diamine 1-N-iminosugars, proposed by us as a new class of iminosugars, have a nitrogen atom in place of the anomeric carbon. Various kinds of 1-N-iminosugars have been synthesized from glyconolactones as a chiral source by the versatile synthetic strategy in a stereospecific fashion and/or by the convergent strategy from siastatin B, a secondary metabolite of Streptomyces. The protonated form of the 1-N-iminosugar mimics the charge at the anomeric position in the transition state of enzymatic glycosidic hydrolysis, resulting in the strong and specific inhibition for glycosidases and glycosyltransferases. They have recently been recognized as a new source of therapeutic drug candidate in a wide range of diseases associated with the carbohydrate metabolism of glycoconjugates such as tumor metastasis, influenza virus infection, inflammatory disease and so forth. This review describes our research progress in synthesis, biological and pharmacological activity, and the therapeutic potentials of gem-diamine 1-N-iminosugar (gem-diamine 1-azasugar).