Several novel oxygenated polyunsaturated lipid mediators biosynthesized from n-3 docosapentaenoic acid were recently isolated from murine inflammatory exudates and human primary cells. These compounds belong to a distinct family of specialized pro-resolving mediators, and display potent in vivo anti-inflammatory and pro-resolution effects. The endogenously formed specialized pro-resolving mediators have attracted a great interest as lead compounds in drug discovery programs towards the development of new classes of drugs that dampen inflammation without interfering with the immune response. Detailed information on the chemical structures, cellular functions and distinct biosynthetic pathways of specialized pro-resolving lipid mediators is a central aspect of these biological actions. Herein, the isolation, structural elucidation, biosynthetic pathways, total synthesis and bioactions of the n-3 docosapentaenoic acid derived mediators PD1n-3 DPA and MaR1n-3 DPA are discussed. In addition, a brief discussion of a novel family of mediators derived from n-3 docosapentaenoic acid, termed 13-series resolvins is included.

Specialized pro-resolving lipid mediators are biosynthesized during the resolution phase of acute inflammation from n-3 polyunsaturated fatty acids. Recently, the isolation and identification of the four novel mediators denoted 13-series resolvins, namely, RvT1 (1), RvT2 (2), RvT3 (3) and RvT4 (4), were reported, which showed potent bioactions characteristic for specialized pro-resolving lipid mediators. Herein, based on results from LC/MS-MS metabololipidomics and the stereoselective synthesis of 13(R)-hydroxy-7Z,10Z,13R,14E,16Z,19Z docosapentaenoic acid (13R-HDPA, 5), we provide direct evidence that the four novel mediators 1–4 are all biosynthesized from the pivotal intermediate 5. The UV and LC/MS-MS results from synthetic 13R-HDPA (5) matched those from endogenously and biosynthetically produced material obtained from in vivo infectious exudates, endothelial cells, and human recombinant COX-2 enzyme. Stereochemically pure 5 was obtained with the use of a chiral pool starting material that installed the configuration at the C-13 atom as R. Two stereoselective Z-Wittig reactions and two Z-selective reductions of internal alkynes afforded the geometrically pure alkene moieties in 5. Incubation of 5 with isolated human neutrophils gave all four RvTs. The results presented herein provide new knowledge on the biosynthetic pathways and the enzymatic origin of RvTs 1–4.

Recent research efforts focusing on the many mechanisms participating in the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators. These endogenous molecules include the lipoxins, resolvins, protectins and maresins, collectively coined specialized pro-resolving mediators (SPMs). SPMs are oxygenated polyunsaturated fatty acids biosynthesized by lipoxygenases and cyclooxygenases enzymes. These chemically sensitive molecules are produced in nano- to pico-gram amounts in vivo and exhibit potent anti-inflammatory and pro-resolving bioactions. In addition, SPMs clear bacterial infections, reduce pain and display bioactivities towards host defense, organ protection and tissue remodeling. Altogether, these bioactions and the need for synthetic SPMs for determination of absolute configuration and in vivo experiments have spurred a great interest in the synthetic and biomolecular communities. This review covers reported stereoselective total syntheses and outlines the most significant bioactions of the E-series resolvins.

Biomolecular investigations using synthetic ePD _{n-3 DPA} have been performed to study its role in the biosynthesis of the specialized pro-resolving mediator PD1 _{n-3 DPA} .