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

J Antibiot (Tokyo). 2009 Aug;62(8):407-23. doi: 10.1038/ja.2009.53. Epub 2009 Jul 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Galactose / chemical synthesis
  • Galactose / pharmacology
  • Glucose / metabolism*
  • Humans
  • Imino Pyranoses / chemical synthesis
  • Imino Pyranoses / pharmacology
  • Indicators and Reagents
  • Influenza, Human / drug therapy
  • Lysosomal Storage Diseases / drug therapy
  • Mice
  • Neoplasm Metastasis / drug therapy
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Imino Pyranoses
  • Indicators and Reagents
  • galactose-type gem-diamine 1-N-iminosugar
  • Glucose
  • Galactose