Stereoselective Synthesis,Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2n-3 DPA |
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| Authors: | Amalie F Reinertsen Dr Karoline G Primdahl Roberta De Matteis Prof Jesmond Dalli Prof Trond V Hansen |
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| Institution: | 1. Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, P.O. Box 1068, 0316 Oslo, Norway;2. Lipid Mediator Unit, Center for Biochemical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ United Kingdom |
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| Abstract: | Herein we report the first total synthesis of RvD2n-3 DPA, an endogenously formed mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid. The key steps are the Midland Alpine borane reduction, Sonogashira cross-coupling reactions, and a Z-selective alkyne reduction protocol, yielding RvD2n-3 DPA methyl ester in 13 % yield over 12 steps (longest linear sequence). The physical property data (UV chromophore, chromatography and MS/MS fragmentation) of the synthetic lipid mediator matched those obtained from biologically produced material. Moreover, synthetic RvD2n-3 DPA also carried the potent biological activities of enhancing macrophage uptake of Staphylococcus aureus and zymosan A bioparticles. |
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| Keywords: | n-3 docosapentaenoic acid resolution of bacterial infection and inflammation resolvins RvD2n-3 DPA specialized pro-resolving mediators |
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