Psiguadiols A–J, Rearranged Meroterpenoids as Potent PTP1B Inhibitors from Psidium guajava

Psiguadiols A–J (1–10), new meroterpenoids with rearranged skeletons, were isolated from the leaves of Psidium guajava. Compounds 1–3 represent the first examples of 6,8-diformyl-5,7-dihydroxy-4-phenylchromane-coupled sesquiterpenoids with an unprecedented C-8-spiro-fused 6/6/9/4 tetracyclic ring system. Compounds 4 and 5 represent two unusual scaffolds featuring 1β,6β- and 3α,5α-epoxy rings, respectively. The combination of spectroscopic data analyses, comparison of experimental and calculated ECD data, and single-crystal X-ray diffraction data of 1, 6, and 8 allowed for the assignment of the structures. A putative biosynthetic pathway for 1–10 is discussed. Compounds 1, 7, and 8 exhibited inhibitory activities against PTP1B with IC50 values of 4.7, 6.2, and 9.2 μM, respectively. In addition, molecular docking was performed to investigate the mechanism of action.