Grandifolins A-D: three 6/6/5 abietane diterpenes and an abietane diterpene from Salvia grandifolia.

The genus Salvia is a well-established source of biologically active compounds with beneficial health effects. In this study, we aimed to isolate and structurally characterize novel compounds from Salvia grandifolia and evaluate their cytotoxic activity against human promyelocytic leukemia (HL-60) and cervical cancer (HeLa) cell lines. Three new rearranged abietane-type diterpenes, grandifolins A-C (1-3) and a new abietane diterpene, grandifolin D (4), were isolated from the roots of Salvia grandifolia, along with 12 known compounds (5-16). Their structures were determined by combining extensive ¹H and ¹³C spectroscopy, X-ray crystallography, and electronic circular dichroism spectra (ECD). The skeletons of 1-3 had a rearranged structure with a 6/6/5 ring from an abietane-type diterpene. A plausible biosynthetic pathway for the rearranged skeleton was also proposed. Many of the isolated compounds showed weak cytotoxicity against HeLa or HL-60 cell lines.