Chu Hang, Dünstl Georg, Felding Jakob, Baran Phil S
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.
Research & Development, LEO Pharma, A/S Industriparken 55, 2750 Ballerup, Denmark.
Bioorg Med Chem Lett. 2018 Sep 1;28(16):2705-2707. doi: 10.1016/j.bmcl.2018.03.065. Epub 2018 Mar 23.
Thapsigargin (3) is a potent inhibitor of the SERCA-pump protein, with potential for application in a variety of medicinal areas. The efficient and scalable syntheses of thapsigargin (3) and nortrilobolide (2) have been disclosed previously. To demonstrate the modularity of the previous routes, three natural products (compounds 6, 13, 15) and four analogs (compounds 17-20) have been divergently prepared from a common building block featuring varied acyl chains at the C2, C3, and C8 positions. Biological tests revealed that all of the compounds prepared displayed promising activity profiles.
毒胡萝卜素（3）是一种有效的肌浆网Ca2+-ATP酶泵蛋白抑制剂，具有在多种医学领域应用的潜力。毒胡萝卜素（3）和去甲三裂叶豚草素（2）的高效且可扩展的合成方法此前已被公开。为了证明先前路线的模块化，已从一个在C2、C3和C8位具有不同酰基链的通用结构单元出发，发散性地制备了三种天然产物（化合物6、13、15）和四种类似物（化合物17 - 20）。生物学测试表明，所制备的所有化合物都显示出有前景的活性概况。
