Rearranged Diels–Alder Adducts and Prenylated Flavonoids as Potential PTP1B Inhibitors from <i>Morus nigra</i>

Abstract

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).