Visible‐Light Photocatalyzed Skeletal Rearrangement Enables the Synthesis of Highly Functionalized Xanthenes with Antitumor Activity

作者：Shi-Lin Lin, Fen Zhao, Fen Wei, Yi‐Zhong Shi, Jing Wen, Chao Yang, H. ZHANG, Chuang‐Chuang Li, Chang Liu, Chang Liu, Wen‐Cai Ye, Min‐Jing Cheng, Min‐Jing Cheng, Lei Wang, Lei Wang · 发表于：Angewandte Chemie International Edition · 年份：2024 · DOI：10.1002/anie.202420671 · 被引用次数：7 · 研究领域：Radical Photochemical Reactions、Catalytic C–H Functionalization Methods、Multicomponent Synthesis of Heterocycles

Highly functionalized xanthenes possess an impressive range of bioactivities and daunting synthetic challenge due to their unique ring systems and stereocenters. Here, we report an unprecedented ketyl radicals-induced skeletal rearrangement reaction of spirodihydrobenzofurans, enabled by zero-valent iron as reducing agents via photoredox catalysis, facilitating the facile preparation of various highly functionalized xanthenes. The features of this protocol include high chemo- and regioselectivity, exceptionally mild conditions, a broad substrate scope, scalability to gram-scale quantities, and consistent delivery of good to excellent yields. Mechanistic studies rationalize the function of this zero-valent iron-based reactivity in radical generation. Notably, this reaction was applied to the first asymmetric total synthesis of the complex polycyclic xanthene ent-myrtucomvalones E-F. Moreover, this work led to the discovery of an agent with highly effective antiosteosarcoma activity in vitro and in vivo, potentially paving the way for the development of new xanthene-based candidates for osteosarcoma treatment.