Maresins lipid mediators

This chapter summarizes recent findings involving the formation and biological roles of several new types of polyunsaturated anti-inflammatory and pro-resolving lipid mediators [1], such as lipoxins, resolvins, protectins, and maresins (MaR). These molecules are able to dampen the inflammatory response, promote the resolution of inflammation, and exhibit other beneficial actions at inflammatory sites [2-4]. 

DHA, a C22 6 omega-3 (co-3) fatty acid, is a major lipid component in the brain and eye [14], and a common ingredient of fish oil. DHA is an extensively stndied PUFA, and its enzymatic oxygenation leads to several series of benehcial lipid mediators (docosanoids), including D-resolvins (RvD) [15], protectins/nenroprotectins (PD/NPD) [16-19], and maresins (MaR) [20-22]. 

This chapter is focused on the biosynthesis and actions of lipoxins, resolvins, protectins, and maresins. Each group of PUFA-derived lipid mediators has its own distinct biosynthetic pathways and features a specialized biological activity profile. 

A large number of studies on the biological actions of the lipoxins and their stable analogs revealed the multi-faceted biological roles of this class of lipid mediators [8,10,11,27,28,30,31,35,37-63], Selected examples of applications in various disease models are summarized in the section Beneficial Roles of Lipoxins, Resolvins, Protectins, and Maresins (Table 9.1). 

The maresins (MaR) are lipid mediators generated from DHA in macrophages and have beneficial actions by enhancing resolution. The name maresin was coined to indicate that they are macrophage mediators that raolve inflammation [20]. 

The lipid mediators derived from ARA, EPA, and DHA discussed above (i.e., lipox-ins, resolvins, protectins, and maresins) have different biosynthetic origins and variable overall bioactivity profiles. These molecules have been collectively termed specialized pro-resolving lipid mediators (SPM), due to their conunon biological role, namely their ability to reduce the inflanunatory response, and to promote the resolution of inflammation and return to homeostasis. 

More recent applications of the Sonogashira reaction in PUFA synthesis include Spurs and Rodriguez s synthesis of maresin 1 (56) [72], a potent anti-inflammatory lipid mediator derived from DHA (7). As shown in Scheme 3.21, the Sonogashira cross coupling reaction of alkyne 82, bearing an unprotected secondary alcohol, with vinyl iodide 83, provided compound 84. Then, removal of the TES group, Boland reduction of the triple bond, and subsequent hydrolysis of the methyl ester afforded maresin 1 (56). 

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