Hyperperins A–X, fusicoccane diterpenoids including an unreported 5/7/5/3 tetracyclic carbon skeleton from Hypoestes purpurea and their T-type calcium channel inhibitory activity

Two unprecedented rearranged fusicoccane diterpenoids, hyperperins A (1) and B (2), and twenty-two new fusicoccane diterpenoids, hyperperins C–X (3–24), were isolated from the aerial parts of Hypoestes purpurea, as well as one known analog (25). The structures and absolute configurations of all newly isolated compounds were determined through comprehensive analyses, including NMR spectroscopy, HR-ESI-MS, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Structurally, compounds 1 and 2 were characterized by a previously unreported carbon skeleton featuring a 5/7/5/3 tetracyclic ring system. Compounds 19 and 20 represent the first examples of fusicoccane diterpenoids with epoxy groups at C-2/C-6 and C-6/C-7, respectively. A plausible biosynthesis pathway for compounds 1 and 2 was proposed. Additionally, compounds 1, 2, 3, 7, and 25 exhibited potent inhibitory activity against the Ca_v3.1 calcium channel with IC₅₀ values of 15.06 ± 1.19, 9.00 ± 1.04, 6.04 ± 0.67, 14.00 ± 1.20, and 6.26 ± 0.82 μmol·L⁻¹, respectively. These findings enrich the structural diversity of fusicoccane diterpenoids and provide promising lead compounds for the development of Ca_v3.1 calcium channel inhibitors.