Stereoselective synthesis of the glycosidase inhibitor australine through a one-pot, double-cyclization strategy

Org Lett. 2007 Jan 4;9(1):77-80. doi: 10.1021/ol062570v.

Abstract

[reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The chiral starting materials were ketone 3, derived from L-erythrulose, and alpha-alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was the highly stereoselective aldol reaction between 4 and a Z boron enolate derived from 3. Another key step was the one-pot construction of the bicyclic pyrrolizidine system by means of a three-step sequence of SN2 displacements induced by benzylamine on a trimesylate precursor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry
  • Cyclization
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Glycoside Hydrolases / metabolism
  • Ketones / chemistry
  • Molecular Structure
  • Pyrrolizidine Alkaloids / chemical synthesis*
  • Pyrrolizidine Alkaloids / chemistry
  • Stereoisomerism

Substances

  • Aldehydes
  • Enzyme Inhibitors
  • Ketones
  • Pyrrolizidine Alkaloids
  • australine
  • Glycoside Hydrolases