Total Synthesis of the Lipid Mediator PD1n-3 DPA: Configurational Assignments and Anti-inflammatory and Pro-resolving Actions
Tungen, Jørn E.
Cheng, Chien-Yee C.
Hansen, Trond V.
MetadataShow full item record
CitationAursnes, Marius, Jørn E. Tungen, Anders Vik, Romain Colas, Chien-Yee C. Cheng, Jesmond Dalli, Charles N. Serhan, and Trond V. Hansen. 2014. “Total Synthesis of the Lipid Mediator PD1n-3 DPA: Configurational Assignments and Anti-inflammatory and Pro-resolving Actions.” Journal of Natural Products 77 (4): 910-916. doi:10.1021/np4009865. http://dx.doi.org/10.1021/np4009865.
AbstractThe polyunsaturated lipid mediator PD1n-3 DPA (5) was recently isolated from self-resolving inflammatory exudates of 5 and human macrophages. Herein, the first total synthesis of PD1n-3 DPA (5) is reported in 10 steps and 9% overall yield. These efforts, together with NMR data of its methyl ester 6, confirmed the structure of 5 to be (7Z,10R,11E,13E,15Z,17S,19Z)-10,17-dihydroxydocosa-7,11,13,15,19-pentaenoic acid. The proposed biosynthetic pathway, with the involvement of an epoxide intermediate, was supported by results from trapping experiments. In addition, LC-MS/MS data of the free acid 5, obtained from hydrolysis of the synthetic methyl ester 6, matched data for the endogenously produced biological material. The natural product PD1n-3 DPA (5) demonstrated potent anti-inflammatory properties together with pro-resolving actions stimulating human macrophage phagocytosis and efferocytosis. These results contribute new knowledge on the n-3 DPA structure–function of the growing numbers of specialized pro-resolving lipid mediators and pathways.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14065546
- HMS Scholarly Articles