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 ones (8–9), were isolated from the South China Sea soft coral Sinularia pedunculata. Their structures were elucidated by extensive spectroscopic analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) approach and X-ray diffraction analysis. Among them, compounds 3 and 4 were rare cembrane diterpenoids that featured a tetrahydropyran moiety with 5, 8-ether linkage and 4,8-ether linkage, respectively, while compounds 4 and 9 inhibited HBV DNA replication with IC₅₀ values of 0.87 and 1.15 μM in HepAD38, respectively. Mechanism investigation suggested that compound 9 accelerated the formation of capsid, but did not affect the levels of HBV cccDNA, total RNA, and pgRNA.