Total Synthesis, Assignment of Absolute Stereochemistry, and Structural Revision of Chlorofusin
Wen-Jian Qian, Wan-Guo Wei, Yong-Xia Zhang, and Zhu-Jun Yao*
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
Abstract: The first total synthesis of chlorofusin was accomplished in a convergent fashion. With all four unambiguous diastereomeric model chromophores as references, the absolute stereochemistry of the chlorofusin chromophore was determined and revised to be (4S,8R,9S) by 1H NMR studies and asymmetric synthesis. This allows the complete structure of natural chlorofusin to be assigned for the first time. Enantioselective copper-mediated oxidation of 4, mild coupling of azaphilone 2 with the free amine-bearing cyclopeptide 3, and a one-pot three-step protocol for the final spiro-aminal formation were successfully achieved with high efficiency to yield the correct stereochemical product 1a.