- Total synthesis of the anti-inflammatory and pro-resolving lipid mediator MaR1n-3 DPA utilizing an sp(3) -sp(3) Negishi cross-coupling reaction.
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 (Weinheim an der Bergstrasse, Germany) (2014-09-17)
Jørn Eivind Tungen, Marius Aursnes, Jesmond Dalli, Hildur Arnardottir, Charles Nicholas Serhan, Trond Vidar Hansen
PMID25225129
초록
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.
MATERIALS