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

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.

SUBMITTER: Tungen JE

PROVIDER: S-EPMC4232850 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Tungen Jørn Eivind JE Aursnes Marius M Dalli Jesmond J Arnardottir Hildur H Serhan Charles Nicholas CN Hansen Trond Vidar TV

Chemistry (Weinheim an der Bergstrasse, Germany) 20140915 45

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. ...[more]

PMID: 25225129

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