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Total Synthesis of the Anti‐inflammatory and Pro‐resolving Lipid Mediator MaR1n−3 DPA Utilizing an sp3–sp3 Negishi Cross‐Coupling Reaction |
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| Authors: | Jørn Eivind Tungen Dr Marius Aursnes Dr Jesmond Dalli Dr Hildur Arnardottir Prof?Dr Charles Nicholas Serhan Prof?Dr Trond Vidar Hansen |
| Institution: | 1. School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO Box 1068 Blindern, 0316 Oslo (Norway);2. Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115 (USA) |
| 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 sp3–sp3 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 |