Salvicsite A-C: Three Seco-Norabietane Diterpenoids Including an Unusual Tetracyclic Skeleton from Salvia castanea Diels f. tomentosa Stib

Three seco-norabietane diterpenoids, salvicsites A-C (1-3), along with two known compounds, were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Salvicsite A (1) represents an unprecedented structural combination, featuring an eight-membered α-methyl-α,β-unsaturated lactone ring and a five-membered α,β-unsaturated lactone ring, based on a 6/6/5/8 ring system. Their structures were elucidated through comprehensive spectroscopic analyses, X-ray crystallography, and quantum chemical calculations. Putative biosynthetic pathways of 1-3 were proposed, with compound 5 being the plausible biogenetic precursor. The AChE inhibition assay demonstrated that salvicsite A (1) exhibited a notable inhibitory effect against AChE, with an IC₅₀ value of 9.56 ± 1.05 μM. Enzymatic kinetic studies indicated that salvicsite A (1) acted as a mixed-type inhibitor, and its binding mode was explored through molecular docking. The results of the cytotoxic activity demonstrated that only compound 5 exhibited inhibitory activity.