Reinertsen Amalie Føreid, Primdahl Karoline Gangestad, Shay Ashley Elizabeth, Serhan Charles Nicholas, Hansen Trond Vidar, Aursnes Marius
Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, P.O. Box 1068, 0316 Oslo, Norway.
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, Massachusetts 02115, United States.
J Org Chem. 2021 Feb 19;86(4):3535-3545. doi: 10.1021/acs.joc.0c02913. Epub 2021 Feb 3.
Herein, we report the stereoselective and convergent synthesis of resolvin E4, a newly identified specialized pro-resolving mediator. This synthesis proves the absolute configuration and exact olefin geometry. Key elements of the successful strategy include a highly stereoselective MacMillan organocatalytic oxyamination, a Midland Alpine borane reduction, and the use of a 1,4-pentadiyne unit as a linchpin building block. The application of reaction telescoping in several of the synthetic transformations enabled the preparation of the resolvin E4 methyl ester in 10% yield over 10 steps (longest linear sequence). The physical property (UV-Vis and LC-MS/MS) data of synthetic resolvin E4 matched those obtained from biologically produced material.
在此，我们报道了新鉴定的特殊促消退介质消退素E4的立体选择性和汇聚合成。该合成确定了其绝对构型和确切的烯烃几何结构。成功策略的关键要素包括高度立体选择性的麦克米伦有机催化氧胺化反应、米德兰阿尔派硼烷还原反应，以及使用1,4-戊二炔单元作为关键构建模块。在几个合成转化步骤中应用反应串联，使得能够在10步反应（最长线性序列）中以10%的产率制备消退素E4甲酯。合成的消退素E4的物理性质（紫外可见光谱和液相色谱-串联质谱）数据与从生物产生的物质中获得的数据相匹配。
