Herein, we report the stereoselective
and convergent synthesis
of resolvin E4, a newly identified specialized pro-resolving mediator.
This synthesis proves the absolute configuration and exact olefin
geometry. Key elements of the successful strategy include a highly
stereoselective MacMillan organocatalytic oxyamination, a Midland
Alpine borane reduction, and the use of a 1,4-pentadiyne unit as a
linchpin building block. The application of reaction telescoping in
several of the synthetic transformations enabled the preparation of
the resolvin E4 methyl ester in 10% yield over 10 steps (longest linear
sequence). The physical property (UV–Vis and LC–MS/MS)
data of synthetic resolvin E4 matched those obtained from biologically
produced material.
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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