ent-Kaurane-Based Diterpenoids, Dimers, and Meroditerpenoids from Isodon xerophilus

Eight new diterpenoids (1–8) with varied structures were isolated from the aerial parts of Isodon xerophilus. Among them, xerophilsin A (1) was found to be an unusual meroditerpenoid representing a hybrid of an ent-kauranoid and a long-chain aliphatic ester, xerophilsins B–D (2–4) are dimeric ent-kauranoids, while xerophilsins E–H (5–8) are new ent-kauranoids. The structures of 1–8 were elucidated mainly through the analyses of their spectroscopic data. The absolute configurations of 2, 6, and 8 were confirmed by single-crystal X-ray diffraction, and the configuration of C-16 in 7 was established through quantum chemical calculation of NMR chemical shifts, as well as modeling of key interproton distances. Bioactivity evaluation of all isolated compounds revealed that 2, 3, and 5 inhibited NO production in LPS-stimulated RAW264.7 cells.