Iodine-promoted oxidative cross-coupling for the synthesis of (E)-2-(3-oxo-3-phenylprop-1-en-1-yl)-3-phenylquinazolin-4(3H)-one via C–H activation: development of synthetic TLX agonists

Abstract

We report the development of an efficient iodine-promoted oxidative cross-coupling reaction for the synthesis of (E)-2-(3-oxo-3-phenylprop-1-en-1-yl)-3-phenylquinazolin-4(3H)-one derivatives. This novel methodology facilitates the coupling of methyl ketones with 2-methyl-3-arylquinazolin-4(3H)-ones under mild conditions, delivering high selectivity and excellent yields. The reaction offers a significant advancement in constructing highly conjugated systems, providing a streamlined and sustainable alternative to traditional synthetic approaches. Beyond the innovative chemistry, the synthesized compounds demonstrated agonistic activity for TLX, an orphan nuclear receptor crucial for neural stem cell proliferation, development, and disease. These findings highlight the dual importance of the methodology in enabling sustainable synthesis and the biological relevance of the resulting compounds as potential therapeutic tools.