Stereoselective synthesis of MaR2n-3 DPA

Jeanne Sønderskov; Jørn E Tungen; Francesco Palmas; Jesmond Dalli; Charles N Serhan; Yngve Stenstrøm; Trond Vidar Hansen

doi:10.1016/j.tetlet.2019.151510

Stereoselective synthesis of MaR2_{n-3 DPA}

Tetrahedron Lett. 2020 Feb 13;61(7):151510. doi: 10.1016/j.tetlet.2019.151510. Epub 2019 Dec 9.

Authors

Jeanne Sønderskov¹, Jørn E Tungen², Francesco Palmas³, Jesmond Dalli^{3

4}, Charles N Serhan⁵, Yngve Stenstrøm¹, Trond Vidar Hansen^{1

2}

Affiliations

¹ Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, PO Box 5003, 1432 Ås, Norway.
² Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, PO Box 1068 Blindern, N-0316 Oslo, Norway.
³ 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, UK.
⁴ Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, UK.
⁵ Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Hale Building for Transformative Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States.

Abstract

The first total synthesis of the n-3 docosapentaenoic derived oxygenated product MaR2_{n-3 DPA} has been achieved. The 13R and 14S stereogenic centers were introduced using 2-deoxy-d-ribose in a chiral pool strategy. The geometry of the Z,E,E-triene moiety was prepared using highly E-selective Wittig- and Takai-olefination reactions as well as the Z-stereoselective Lindlar reduction. LC/MS-MS data of synthetic MaR2_{n-3 DPA} matched data for the biosynthetic formed product that enabled the configurational assignment of this oxygenated natural product to be (7Z,9E,11E,13R,14S,16Z,19Z)-13,14-dihydroxydocosa-7,9,11,16,19-pentaenoic acid.

Keywords: MaR2n-3 DPA; Maresins; Specialized pro-resolving mediator; n-3 docosapentaenoic acid.

Abstract

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