Total synthesis of the anti-inflammatory and pro-resolving lipid mediator MaR1n-3 DPA utilizing an sp(3) -sp(3) Negishi cross-coupling reaction

Chemistry. 2014 Nov 3;20(45):14575-8. doi: 10.1002/chem.201404721. Epub 2014 Sep 15.

Abstract

The first total synthesis of the lipid mediator MaR1n-3 DPA (5) has been achieved in 12 % overall yield over 11 steps. The stereoselective preparation of 5 was based on a Pd-catalyzed sp(3) -sp(3) Negishi cross-coupling reaction and a stereocontrolled Evans-Nagao acetate aldol reaction. LC-MS/MS results with synthetic material matched the biologically produced 5. This novel lipid mediator displayed potent pro-resolving properties stimulating macrophage efferocytosis of apoptotic neutrophils.

Keywords: cross-coupling; inflammation; natural products; palladium; total synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology
  • Catalysis
  • Docosahexaenoic Acids / chemical synthesis*
  • Docosahexaenoic Acids / pharmacology
  • Humans
  • Macrophages / drug effects
  • Stereoisomerism

Substances

  • Anti-Inflammatory Agents
  • Docosahexaenoic Acids