Mangrove Tirucallane- and Apotirucallane-Type Triterpenoids: Structure Diversity of the C-17 Side-Chain and Natural Agonists of Human Farnesoid/Pregnane–X–Receptor

摘要

Ten new triterpenoid compounds with structure diversity of the C-17 side-chain, including nine tirucallanes, named xylocarpols A–E (>1–>5) and agallochols A–D (>6–>9), and an apotirucallane, named 25-dehydroxy protoxylogranatin B (>10), were isolated from the mangrove plants Xylocarpus granatum, Xylocarpus moluccensis, and Excoecaria agallocha. The structures of these compounds were established by HR-ESIMS and extensive one-dimensional (1D) and two-dimensional (2D) NMR investigations. The absolute configurations of >1 and >2 were unequivocally determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation; whereas those of >4, >6–>8 were assigned by a modified Mosher’s method and the comparison of experimental electronic circular dichroism (ECD) spectra. Most notably, >5, >6, >7, and >9 displayed potent activation effects on farnesoid–X–receptor (FXR) at the concentration of 10.0 μM; >10 exhibited very significant agonistic effects on pregnane–X–receptor (PXR) at the concentration of 10.0 nM.