Tetrahydropyrrolization of Resveratrol and Other Stilbenes Improves Inhibitory Effects on DNA Oxidation

Abstract

The inhibitory effect of resveratrol on DNA oxidation caused by 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) was found to be enhanced if the C=C bond in resveratrol was converted into tetrahydropyrrole by reaction with azomethine ylide (CH2 =N(+) (CH3 )CH2 (-) ). This encouraged us to explore whether the inhibitory activities of other stilbenes could also be increased by the same method. We found that the inhibitory effects of the tetrahydropyrrole derivatives on AAPH-induced oxidation of DNA were higher than those of the corresponding stilbenes, because the tetrahydropyrrole motif can provide hydrogen atoms to be abstracted by radicals. Therefore, the tetrahydropyrrolization offered an advantage for enhancing the antioxidant effects of stilbenes. Notably, (CH3 )3 SiCH2 N(CH3 )CH2 OCH3 (in the presence of CF3 COOH) and (CH3 )3 NO (in the presence of LiN(iPr)2 ) can be used to generate azomethine ylide for the tetrahydropyrrolization of stilbenes containing electron-withdrawing and -donating groups, respectively.