Direct synthesis of imino-C-nucleoside analogues and other biologically active iminosugars

Nat Commun. 2015 Apr 23:6:6903. doi: 10.1038/ncomms7903.

Abstract

Iminosugars have attracted increasing attention as chemical probes, chaperones and leads for drug discovery. Despite several clinical successes, their de novo synthesis remains a significant challenge that also limits their integration with modern high-throughput screening technologies. Herein, we describe a unique synthetic strategy that converts a wide range of acetaldehyde derivatives into iminosugars and imino-C-nucleoside analogues in two or three straightforward transformations. We also show that this strategy can be readily applied to the rapid production of indolizidine and pyrrolizidine iminosugars. The high levels of enantio- and diastereoselectivity, excellent overall yields, convenience and broad substrate scope make this an appealing process for diversity-oriented synthesis, and should enable drug discovery efforts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Discovery
  • Imines / chemical synthesis*
  • Imino Sugars / chemical synthesis*
  • Indolizidines / chemical synthesis*
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry*

Substances

  • Imines
  • Imino Sugars
  • Indolizidines
  • Nucleosides