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

Iminosugars, which carry a basic nitrogen in the carbohydrate ring, have attracted increasing interest as new glycomimetics. Gem-diamine 1-N-iminosugars, 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 in a totally stereospecific manner and/or by the convergent strategy from siastatin B, a secondary metabolite of Streptomyces. The protonated form of 1-N-iminosugar mimics the charge at the anomeric position in the transition state of enzymatic glycosidic hydrolysis, resulting in a strong and specific inhibition of glycosidases and glycosyltransferases. They have been recently recognized as a new source of therapeutic drug candidates in a wide range of diseases associated with the carbohydrate metabolism of glycoconjugates, such as tumor metastasis, influenza virus infection, lysosomal storage disorder and so forth. The Journal of Antibiotics (2009) 62, 407-423; doi:10.1038/ja.2009.53; published online 3 July 2009