Total Synthesis, Assignment of Absolute Stereochemistry, and Structural Revision of Chlorofusin

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 (4 S,8 R,9 S ) by 1 H 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 .