Solvent-Dependent Chemoselective and Stereoselective Approach to Synthesis of Spiro-γ-Lactams with Potent Anticancer Activity

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. (Figure presented.).