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Total Synthesis of the Antidiabetic (Type 2) Lipid Mediator Protectin DX/PDX

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journal contribution
posted on 26.12.2018, 20:00 by Jean-Yves Sancéau, René Maltais, Donald Poirier, André Marette
The first total synthesis of a lipid mediator derived from natural ω-3-fatty acid docosahexaenoic acid (DHA), 10S,17S-diHDHA (also referred to as protectin DX/PDX), was achieved in a convergent route (29 steps). The two chiral hydroxyl groups at C-10 and C-17 were derived from readily available (S)-1,2,4-butanetriol and (R)-glycidol, respectively. The two stereodefined E-double bonds were generated by a Takai olefination, and the skipped diene side chain was introduced with a stereocontrolled Wittig olefination. Importantly, the sensitive conjugated E,Z,E-triene intermediate was generated by a Boland reduction of the central triple bond of a E,E-dienyne. Overall, this synthetic strategy should allow the preparation of a larger quantity of PDX, which is inaccessible via previously reported biosynthetic approaches.