Solvent controlled synthesis of 2,3-diarylepoxy indenones and α-hydroxy diarylindanones and their evaluation as inhibitors of DNA alkylation repair

Herein, we report a novel and unexpected metal-free oxygenation of 2,3-diphenyl-1-indenones, under an oxygen atmosphere (air), to either 2,3-epoxy-2,3-diphenyl-1-indenone or 2- hydroxy-2,3-diphenyl-1-indanone, depending on the conditions. Several bioactive epoxy indenones and one-pot alpha-hydroxy indanones (alpha-acyloin) were synthesized from 2,3-diaryl dihydroindanone and 2,3-diarylindenone, respectively. A plausible reaction mechanism is also proposed, where oxygenation would take place at the alpha-position and further proton abstraction from the beta-position leads to epoxy indenone derivatives. A one-pot cis-hydroxy indanone protocol is also achieved directly from biaryl indenone via reduction, epimerization, and oxygenation. The synthesized compounds were evaluated for inhibitory activity against the DNA repair protein AlkB. Among the screened (17 tested) compounds, one epoxide derivative was found to be a specific inhibitor of AlkB enzyme function.

Automated summary

A novel metal-free oxygenation reaction was reported, leading to the synthesis of several bioactive epoxy indenones and alpha-hydroxy indanones. The reaction mechanism was proposed, and a one-pot cis-hydroxy indanone protocol was achieved directly from biaryl indenone. The synthesized compounds were evaluated for inhibitory activity against the DNA repair protein AlkB, and one epoxide derivative showed specific inhibitory effects.