What Is the True Structure of D609, a Widely Used Lipid Related Enzyme Inhibitor?

Org Lett. 2016 Feb 19;18(4):768-71. doi: 10.1021/acs.orglett.6b00025. Epub 2016 Feb 8.

Abstract

D609 (1) has been used as a lipid-related enzyme inhibitor during the past three decades. Although it has eight possible stereoisomers, no systematic research considering its chirality has been performed. In this paper, eight possible chiral alcohols as direct precursors of D609 were synthesized, and their stereochemistries were elucidated by a vibrational circular dichroism (VCD) technique. Phosphatidylcholine-specific phospholipase C and sphingomyelin synthase inhibition assays of these isomers showed considerable differences in their activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged-Ring Compounds / chemistry*
  • Bridged-Ring Compounds / pharmacology*
  • Circular Dichroism
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Lipids / chemistry
  • Molecular Structure
  • Norbornanes
  • Stereoisomerism
  • Thiocarbamates
  • Thiones / chemistry*
  • Thiones / pharmacology*
  • Type C Phospholipases / antagonists & inhibitors*

Substances

  • Bridged-Ring Compounds
  • Enzyme Inhibitors
  • Lipids
  • Norbornanes
  • Thiocarbamates
  • Thiones
  • tricyclodecane-9-yl-xanthogenate
  • Type C Phospholipases
  • phosphatidylcholine-specific phospholipase C