Hypoestins A–D: highly modified fusicoccane diterpenoids with promising Cav3.1 calcium channel inhibitory activity from Hypoestes purpurea

Hypoestins A–D (1–4), four highly modified fusicoccane diterpenoids with two unreported carbon skeletons, and hypoestins E (5) and F (6), two previously undescribed fusicoccane diterpenoids, were isolated from the aerial parts of Hypoestes purpurea. Their structures and absolute configurations were characterized by comprehensive spectroscopic, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. Structurally, compounds 1 and 2 are the first cyclopropane-containing fusicoccane diterpenoids with an unreported 5/8/5/3-tetracyclic carbon skeleton. Compounds 3 and 4 possess a rearranged 5/7/5-tricyclic carbon framework. A plausible biosynthetic pathway for 1–4 was proposed. Activity evaluation revealed that 4 is a new class of Cav3.1 calcium channel inhibitor with an IC50 value of 10.35 μM, which would provide a potential lead compound for drug discovery.