Xuetonglactones A-F: Highly Oxidized Lanostane and Cycloartane Triterpenoids From Kadsura heteroclita Roxb. Craib.

Xuetonglactones A-F (1-6), six unreported highly oxidized lanostane- and cycloartane-type triterpenoids along with 22 known scaffolds (7-28) were isolated from the stems of Kadsura heteroclita (Roxb.) Craib. Compared with previous congeners, xuetonglactone A (1), possesses an unprecedented 20,21-α-epoxide, and xuetonglactone D (4) features an unusual 19-α-hydroperoxyl moiety. The structures and the absolute configurations of the compounds were established by extensive one- and two-dimensional NMR, and electronic circular dichroism (ECD) spectroscopic analysis, with those of 1 and 5 confirmed by single-crystal X-ray diffraction technique. Compounds 1 and 2 exhibited inhibition of iNOS activity in LPS-induced macrophages with IC₅₀ values of 22.0, and 17.0 μg/mL, respectively. While compounds 6, 7, 8, and 24 showed potent cytotoxic activities against human cervical cancer cell lines (HeLa) with the IC₅₀ values of 4.0, 5.8, 5.0, and 6.4 μM, and against human gastric cancer cells (BGC 823) with the IC₅₀ values of 2.0, 5.0, 2.5, and 2.0 μM, respectively. Moreover, plausible biogenetic pathways of (1-6) were also proposed.