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

Abstract

Xuetonglactones A-F (<b>1</b>-<b>6</b>), six unreported highly oxidized lanostane- and cycloartane-type triterpenoids along with 22 known scaffolds (<b>7</b>-<b>28</b>) were isolated from the stems of <i>Kadsura heteroclita</i> (Roxb.) Craib. Compared with previous congeners, xuetonglactone A (<b>1</b>), possesses an unprecedented 20,21-α-epoxide, and xuetonglactone D (<b>4</b>) 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 <b>1</b> and <b>5</b> confirmed by single-crystal X-ray diffraction technique. Compounds <b>1</b> and <b>2</b> exhibited inhibition of iNOS activity in LPS-induced macrophages with IC₅₀ values of 22.0, and 17.0 μg/mL, respectively. While compounds <b>6</b>, <b>7</b>, <b>8</b>, and <b>24</b> 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 (<b>1</b>-<b>6</b>) were also proposed.