Chemistry: A European Journal 2014-11-03

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

Jørn Eivind Tungen, Marius Aursnes, Jesmond Dalli, Hildur Arnardottir, Charles Nicholas Serhan, Trond Vidar Hansen

Index: Chemistry 20(45) , 14575-8, (2014)

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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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.