Total Synthesis of Allocyclinone A via Late‐Stage Halogen Swapping

Abstract

ABSTRACT 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.