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Total Synthesis of the Anti‐inflammatory and Pro‐resolving Lipid Mediator MaR1 n −3 DPA Utilizing an sp 3 –sp 3 Negishi Cross‐Coupling Reaction
Author(s) -
Tungen Jørn Eivind,
Aursnes Marius,
Dalli Jesmond,
Arnardottir Hildur,
Serhan Charles Nicholas,
Hansen Trond Vidar
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201404721
Subject(s) - negishi coupling , mediator , lipid signaling , efferocytosis , yield (engineering) , stereoselectivity , total synthesis , sonogashira coupling , chemistry , stereochemistry , medicine , in vitro , macrophage , biochemistry , physics , receptor , catalysis , palladium , thermodynamics
The first total synthesis of the lipid mediator MaR1 n −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.