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

Abstract

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.

Heteroannulation of Arynes with α‐Amino Imides: Synthesis of 2,2‐Disubstituted Indolin‐3‐ones and Application to the Enantioselective Total Synthesis of (+)‐Hinckdentine A

“…Aremarkable feature of the new method is that it allows direct access to the aminoethyl-or aminopropyl-substituted indolin-3-ones found in many bioactive compounds. [16] While the incorporation of the versatile amino group in aside chain is highly beneficial, this is also alimitation of the method. To further extend the general applicability of our approach, we decided to examine other moderately activated carboxylic acid derivatives that are compatible with the presence of an unprotected a-amino group.T his is highly challenging since activated a-amino esters are known to undergo facile dimerization to afford the 2,5-diketopiperazines.…”

“…In light of the importance of the indoxyl structure in natural products, [16] as well as its application as building blocks in organic synthesis [17] and fluorescent dyes, [18] we set out to examine the generality of this heteroannulation method. Thes ynthesis of imides is depicted in Scheme 3.…”

Biosynthetically Inspired Transformation of Iboga to Monomeric Post-iboga Alkaloids

“…21 However, the chippiine-and dippinine-type post-iboga alkaloids 22 have never succumbed to synthesis despite their structure exposure to the synthetic community for over 30 years. 23 Furthermore, a recent outburst of isolation reports of post-iboga alkaloids 11,12,14,17,[24][25][26][27][28][29] rekindled interest in this family of natural products and has been challenging the synthetic community.…”

Three New Monoterpenoid Indole Alkaloids from Ervatamia pandacaqui

“…The genus Ervatamia (Apocynaceae) contains about 120 species all over the world, and 15 of them are distributed in southern China . It has been proven to be good sources of monoterpenoid indole alkaloids (MIAs) . The complex poly‐fused ring system and diversity of stereostructure as well as significant biological activities of MIAs have attracted great interest as challenging targets for total synthesis and biogenetic studies .…”

“…[1] It has been proven to be good sources of monoterpenoid indole alkaloids (MIAs). [2] The complex poly-fused ring system and diversity of stereostructure as well as significant biological activities of MIAs have attracted great interest as challenging targets for total synthesis and biogenetic studies. [3 -5] Pharmacological studies had demonstrated promising anticancer, antiaddiction, antioxidant, and antibacterial activities.…”