Solvent‐Dependent Chemoselective and Stereoselective Approach to Synthesis of Spiro‐γ‐Lactams with Potent Anticancer Activity
Jie Lei, Liu‐Jun He, Dianyong Tang, Jingyuan Wen, Wei Yan, Hongyu Li, Zhong‐Zhu Chen, Zhigang Xu
Abstract
Abstract Chemoselective approaches were developed for derivatizing diastereoselective chromanone spiro‐γ‐lactams through the Michael‐type addition by using amide as a weak nucleophile to construct the spiro‐carbon center under basic conditions. To expand the scope of this post‐Ugi cascade reaction, a new series of oxidized chromone derivatives was synthesized by altering solvent from EtOH to DMF. Compounds 7 a and 7 b which could be synthesized in one day, demonstrated comparable anticancer activities with legendary anticancer drug paclitaxel in the PANC and U87 cell lines. This methodology offers a new approach to construct spiro‐carbon centers with functionalized chromanones or chromones under mild reaction conditions. magnified image