Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, P.O. Box 1068, 0316, Oslo, Norway.
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, United Kingdom.
Chemistry. 2022 Feb 1;28(7):e202103857. doi: 10.1002/chem.202103857. Epub 2021 Dec 28.
Herein we report the first total synthesis of RvD2 , an endogenously formed mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid. The key steps are the Midland Alpine borane reduction, Sonogashira cross-coupling reactions, and a Z-selective alkyne reduction protocol, yielding RvD2 methyl ester in 13 % yield over 12 steps (longest linear sequence). The physical property data (UV chromophore, chromatography and MS/MS fragmentation) of the synthetic lipid mediator matched those obtained from biologically produced material. Moreover, synthetic RvD2 also carried the potent biological activities of enhancing macrophage uptake of Staphylococcus aureus and zymosan A bioparticles.
在此，我们报告了内源性介质 RvD2 的首次全合成，该介质由 ω-3 脂肪酸 n-3 二十二碳五烯酸生物合成。关键步骤是米德兰阿尔卑斯山硼烷还原、Sonogashira 交叉偶联反应和 Z-选择性炔烃还原方案，经过 12 步（最长线性序列）以 13%的收率得到 RvD2 甲酯。合成脂质介质的物理性质数据（紫外发色团、色谱和 MS/MS 碎裂）与从生物产生的物质获得的数据相匹配。此外，合成的 RvD2 还具有增强巨噬细胞摄取金黄色葡萄球菌和酵母聚糖 A 生物颗粒的强大生物学活性。
