Ervatamines A-I, Anti-inflammatory Monoterpenoid Indole Alkaloids with Diverse Skeletons from Ervatamia hainanensis

Nine new monoterpenoid Indole Alkaloids, ervatamines A-I (1-9), and five known ones (10-14), were isolated from Ervatamia hainanensis. The new structures were elucidated by extensive spectroscopic analysis and comparison to known compounds. Their absolute configurations were determined by various methods including computational methods, X-ray diffraction analysis, and electronic circular dichroism spectroscopy, as well as chemical transformations. Ervatamine A (1) is a ring-C-contracted ibogan-type monoterpenoid indole alkaloid with an unusual 6/5/6/6/6 pentacyclic rearranged ring system. Ervatamines B-E (2-5) display a nitrogen-containing 9/6 ring system, which is rarely observed in nature. The epimeric ervatamines B (2) and C (3) possess a 22-nor-monoterpenoid indole alkaloid carbon skeleton, which was only found in deformylstemmadenine. Compounds 10 and 14 exhibited significant anti-inflammatory activities, with IC50 values of 25.5 and 41.5 μM, respectively, while the IC50 value of indomethacin as a positive control was found to be 42.6 μM. Additionally, compound 9 showed mild activity against 786-O and HL-60 cell lines.