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

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 K 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 M; 10 exhibited very significant agonistic effects on pregnane-X-receptor (PXR) at the concentration of 10.0 nM.