A comparative study of synthetic approaches towards total synthesis of histrionicotoxin: a selective inhibitor of nicotinic acetylcholine receptors

J Asian Nat Prod Res. 2021 Oct;23(10):919-937. doi: 10.1080/10286020.2020.1810670. Epub 2020 Aug 24.

Abstract

The aim of this review is to provide a critical and comparative account of the total synthetic approaches toward histrionicotoxins, alkaloids isolated from skin extracts of Colombian poison arrow frog Dendrobates histrionicus. We have summarized the maneuvers in each paper by graphically detailing the synthesis and associated reaction niceties of only the key intermediates by different researchers. Fascinating structural feature of histrionicotoxins is "8-hydroxy-l-azaspiro[5.5]undecane core" with two side chains at C-2 and C-7 which differ in their length and nature of unsaturation. All synthetic approaches to histrionicotoxins aim at the construction of key intermediate "azaspiro[5.5]undecane ring" and installation of side chains at C-2 and C-7.

Keywords: Histrionicotoxin; nicotinic acetylcholine receptors; synthetic approaches.

Publication types

  • Review

MeSH terms

  • Amphibian Venoms*
  • Animals
  • Anura / metabolism
  • Molecular Structure
  • Receptors, Nicotinic* / metabolism

Substances

  • Amphibian Venoms
  • Receptors, Nicotinic
  • histrionicotoxin