Rearranged phenylpropanoyl-phloroglucinol dimers from the flowers of Xanthostemon chrysanthus

Seven rearranged phenylpropanoyl-phloroglucinol (PPG) dimers, xanthchrysones D-J (1-7), were isolated from the flowers of Xanthostemon chrysanthus. Their structures and absolute configurations were unambiguously established by comprehensive NMR spectroscopy, X-ray crystallography, and quantum chemical calculations. Structurally, compounds 1 and 2 represent the first examples of phenylpropanoyl-phloroglucinol dimers featuring an unprecedented 3-(cyclopentyl(phenyl)methyl)-2-styryl-4H-chromene scaffold, while compounds 3 and 4 incorporate a distinctive 5-(3-phenylpropanoyl)-3,9-dihydrocyclopenta[b]chromen-1(2H)-one backbone. These compounds possess unprecedented skeletons characterized by a unique rearrangement process involving cyclopentanone ring formation and cleavage of the phenylpropanoyl moiety, and their plausible biogenetic pathway was also proposed. All isolates exhibited potent α-glucosidase inhibitory activities, with 5- to 20-fold greater potency than the clinically used antidiabetic drug acarbose. Among them, compounds 6 and 7 showed the most pronounced inhibitory effects, and were therefore selected for subsequent enzyme kinetics studies, molecular docking, and molecular dynamics simulations. Both in vitro and in silico results consistently demonstrated that compounds 6 and 7 are promising candidates for the development of new α-glucosidase inhibitors.