Amentotaxins C–V, Structurally Diverse Diterpenoids from the Leaves and Twigs of the Vulnerable Conifer Amentotaxus argotaenia and Their Cytotoxic Effects

A phytochemical investigation of the MeOH extract of the leaves and twigs of Amentotaxus argotaenia, a relict vulnerable coniferous species endemic to China, led to the isolation and characterization of 35 diterpenoids/norditerpenoids. Twenty of these are new, including 11 ent-kaurane-type (amentotaxins C–M, 1–11, respectively), three icetexane-type [= 9(10→20)abeo-abietane-type (amentotaxins N–P, 12–14, respectively)], four ent-labdane-type (amentotaxins Q–T, 15–18, respectively), and two isopimarane-type [amentotaxins U (19) and V (20)] compounds. Their structures were elucidated on the basis of spectroscopic data, single-crystal X-ray diffraction, the modified Mosher’s method, and electronic circular dichroism data analyses. Compounds 1–9 are rare 18-nor-ent-kaurane-type diterpenoids featuring a 4β,19-epoxy ring. All the isolates were evaluated for their cytotoxic effects against a small panel of cultured human cancer cell lines (HeLa, A-549, MDA-MB-231, SKOV3, Huh-7, and HCT-116), and some of them exhibited cytotoxicities with IC50 values ranging from 1.5 to 10.0 μM.