Highly oxygenated cembrane diterpenoids from the South China Sea soft coral Sinularia pedunculata and their anti-HBV activities

Eleven new highly oxygenated cembrane-type diterpenoids (1−7 and 10−13) and two known analogues (8−9) were isolated from the South China Sea soft coral Sinularia pedunculata. Their structures were determined through extensive spectroscopic analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) approach and X-ray diffraction analysis. Notably, compounds 3 and 4 were rare cembrane diterpenoids featuring a tetrahydropyran moiety with 5,8-ether and 4,8-ether linkages, respectively, while compounds 4 and 9 inhibited HBV DNA replication with IC₅₀ values of 0.87 and 1.15 μmol·L⁻¹ in HepAD38 cells, respectively. Mechanism investigation suggested that compound 9 accelerated capsid formation without affecting the levels of HBV cccDNA, total RNA, or pgRNA.