Total Synthesis of Allocyclinone A via Late-Stage Halogen Swapping.

Allocyclinones A-D are small congeners of angucyclinones with several unusual structural features and potent antibiotic activity against various Gram-positive pathogens. Allocyclinone A, the most active congener, contains an intriguing aromatic trichloromethyl substituent that has never been observed in other natural products before. In this study, we report a modular total synthesis of allocyclinones A and B featuring the convergent assembly of three key building blocks through Hauser annulation and cross-couplings. The synthesis of allocyclinone A was made possible by the application of a late-stage trifluoromethyl-to-trichloromethyl swap, providing a potentially generalizable strategy for aromatic trichloromethyl installation in complex settings. The antibiotic activity of the scaffold was also verified, and attempts to elucidate its mode of action were performed.