Resolving Inflammation: Synthesis,Configurational Assignment,and Biological Evaluations of RvD1n−3 DPA期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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Resolving Inflammation: Synthesis,Configurational Assignment,and Biological Evaluations of RvD1n−3 DPA

Authors:	Dr Jørn Eivind Tungen Dr Lisa Gerstmann Prof Dr Anders Vik Roberta De Matteis Dr Romain Alexandre Colas Prof Dr Jesmond Dalli Prof Dr Nan Chiang Prof Dr Charles Nicholas Serhan Prof Dr Markus Kalesse Prof Dr Trond Vidar Hansen

Institution:	1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, PO Box 1068, 0316 Oslo, Norway;2. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, PO Box 1068, 0316 Oslo, Norway Institute for Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover and Centre of Biomolecular Drug Research (BMWZ), Schneiderberg 38, 30167 Hannover (Germany), Helmholtz Centre for Infection Research GmbH (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany;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. Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115 USA;5. Institute for Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover and Centre of Biomolecular Drug Research (BMWZ), Schneiderberg 38, 30167 Hannover (Germany), Helmholtz Centre for Infection Research GmbH (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany

Abstract:	New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro-resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro-resolving mediator RvD1_{n−3 DPA} has been achieved using the underutilized sp³–sp³ Negishi cross coupling reaction and an alkyne hydrosilylation–protodesilylation protocol. Biological evaluations revealed that this novel mediator displays low nanomolar pro-resolving properties and potently activates the human DRV1/GPR32 receptor. As such, this endogenous natural product is a lead compound for the development of novel immunoresolvents.

Keywords:	Karstedt's catalyst natural products sp3–sp3 cross-coupling specialized pro-resolving mediators total synthesis

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