Cleavage of α-Dicarbonyl Compounds by Terpene Hydroperoxide

Abstract

The highly reactive α-dicarbonyl compounds, glyoxal, methylglyoxal (MGO), and 3-deoxyglucosone, react with the amino groups of proteins to form advanced glycation end-products (AGEs) which have been implicated in diabetic complications, aging, and Alzheimer's disease. We found that a test sample of terpinen-4-ol (T4) containing hydroperoxides showed cleaving activity toward an α-dicarbonyl compound, but that the freshly isolated pure sample did not. Prepared terpinen-4-ol hydroperoxide (T4-H) also efficiently cleaved the C-C bond of the α-dicarbonyl compounds via Baeyer-Villiger-like rearrangement and subsequent hydrolysis of an acid anhydride moiety in the rearranged product to give carboxylic acids. Other terpene hydroperoxides, as well as T4-H, showed significant cleaving activities, and all these hydroperoxides protected RNase A from the lowering of enzyme activity induced by MGO. The cleaving mechanism via Baeyer-Villiger-like rearrangement was confirmed by time-interval NMR measurements of the reaction mixture of the symmetrical α-dicarbonyl compound, diacetyl with T4-H.