First total synthesis of fuzanins C, D and their analogues as anticancer agents†
The first total synthesis of fuzanins C and D, isolated from the culture supernatant of Kitasatospora sp. IFM10917, is described. Key features of this synthetic strategy involve the use of Sharpless asymmetric epoxidation, dihydroxylation, Mitsunobu reaction and Julia-Kocienski olefination. The total synthesis reported herein also confirmed the absolute configuration of fuzanin D. The optical rotations of synthesized fuzanin D and natural product were opposite in sign, leading to a revision of the reported structure as its enantiomer which is further confirmed by molecular modeling studies. In addition, we also synthesized the analogues of fuzanins C, D containing the quinoline nucleus. All of the synthesized compounds were screened for anticancer activity on four cell lines and found to be potent against HT29 colon cancer cell lines, whereas they were found to be less potent against cervical and breast cancer cell lines.