Total Synthesis of Pleofugin A, a Potent Inositol Phosphorylceramide Synthase Inhibitor

Org Lett. 2018 Aug 3;20(15):4637-4640. doi: 10.1021/acs.orglett.8b01930. Epub 2018 Jul 23.

Abstract

X-ray analysis and total synthesis of 1 unambiguously confirmed pleofingin A's absolute configuration. The total synthesis was achieved by convergent assembly of three fragments (12, 14, and 18). This synthetic approach provides access to derivatives of 1 to search for antifungal agents that will be more effective in clinical use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis*
  • Crystallization
  • Cyclization
  • Depsipeptides / chemical synthesis*
  • Glycosphingolipids / chemistry*
  • Hexosyltransferases / antagonists & inhibitors*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Saccharomyces cerevisiae / drug effects
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Depsipeptides
  • Glycosphingolipids
  • inositolphosphorylceramide
  • Hexosyltransferases
  • phosphatidylinositol-ceramide phosphoinositol transferase