Simple and Efficient Synthesis of Anithiactins A-C, Thiasporine A and Their Potent Antitumor 2,4-Linked Oligothiazole Derivatives

Directly 2,4-linked oligothiazoles are not only broadly applied in drug discovery but also are the core structural motif of many biological natural products. With this background, we reported a simple and efficient route for the synthesis of four 2-phenylthiazole natural products anithiactins A-C, thiasporine A, and series of their novel 2,4-linked oligothiazole derivatives relies on the one-pot cascade reaction of beta-azido disulfides and commercially carboxyl acids. This approach also represented a remarkably direct and simple route for 2,4-linked oligothiazoles synthesis. By doing so, ten bisthiazoles and terthiazoles were effectively obtained in only 3 similar to 6 linear steps with good to moderate yields. The bioassay results demonstrated that all the phenyl-based oligothiazoles show potent antitumor activities. Among them, terthiazole 28 was the most potent compound with IC50 values of 4.4 mu M, 4.8 mu M against HCT116 and A549 cell lines, respectively.