Synthesis of Selagibenzophenone A and Its Derivatives for Evaluation of Their Antiproliferative, ROR gamma Inverse Agonistic, and Antimicrobial Effect
Abstract
We report a modular synthetic approach towards novel derivatives of the naturally occurring arylated benzophenone selagibenzophenone A. The initial strategy for the construction of the carbon framework of the derivatives relied on the Suzuki reaction of 2,4,6-tribromobenzonitrile, and the addition of the aryl lithium species to nitrile to generate imine.
However, the formed imines showed remarkable stability toward hydrolysis. Therefore, Suzuki cross-coupling was carried out with 2,4,6-tribromobenzaldehyde and the subsequent addition of organometallic species to the aldehyde.
Oxidation of the resulting alcohol ensured the access to desired ketones. The importance of the developed modular strategy is underlined by the discovery of several derivatives with selective cytotoxic effects and potential anti-inflammatory activity superior to the effect of the natural product. (RORγ = retinoic acid receptor-related orphan receptor-gamma.)