Rearranged Diels–Alder Adducts and Prenylated Flavonoids as Potential PTP1B Inhibitors from Morus nigra

Two novel rearranged Diels-Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A-D (3-6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7 and 8) and two 2-arylbenzofurans (9 and 10). Morunigrines A (1) and B (2) are a novel class of Diels-Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone-stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6 was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1 and 2 is also proposed. Compounds 1 and 2 exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.8 ± 0.2 and 1.3 ± 0.3 μM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 μM).