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Synthesis of N ‐Carbonyl Acridanes as Highly Potent Inhibitors of Tubulin Polymerization via One‐Pot Copper‐Catalyzed Dual Arylation of Nitriles with Cyclic Diphenyl Iodoniums
Author(s) -
Peng Xiaopeng,
Li Ling,
Ren Yichang,
Xue Huanxin,
Liu Jin,
Wen Shijun,
Chen Jianjun
Publication year - 2020
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201901460
Subject(s) - chemistry , aryl , combinatorial chemistry , alkyl , catalysis , polymerization , organic chemistry , polymer
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.