Synthesis of <i>N</i>‐Carbonyl Acridanes as Highly Potent Inhibitors of Tubulin Polymerization <i>via</i> One‐Pot Copper‐Catalyzed Dual Arylation of Nitriles with Cyclic Diphenyl Iodoniums
Xiaopeng Peng, Ling Li, Yichang Ren, Huanxin Xue, Jin Liu, Shijun Wen, Jianjun Chen
Abstract
Abstract A novel Copper‐catalyzed cascade reaction between six‐membered cyclic diaryliodonium salts and nitriles is reported for the facile access to a variety of N ‐carbonyl acridanes in good to excellent yields (up to 82%). The reaction is efficient and atom‐economical with a broad substrate scope (e. g. both aryl / alkyl nitriles and substituted / unsubstituted cyclic diaryliodonium salts compatible in the system). This method is particularly useful for the synthesis of substituted N ‐carbonyl acridanes which are present in many pharmaceutically important compounds, but are not easy to obtain in conventional approaches. Furthermore, one of the newly synthesized acridanes displayed high antiproliferative activity against MB‐468 cancer cells (IC 50 =26 nM, comparable to paclitaxel and colchicine) by inhibiting tubulin polymerization. Together, these findings might grant a rapid access to a novel molecular scaffold with potential anticancer utilities. magnified image