Recent Syntheses of Frog Alkaloid Epibatidine

Author(s)

de Oliveira Filho, Ronaldo E. ^[1] ; Omori, Alvaro T. ^[1]

Affiliation

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

• Document type: Journal article
• Source: Journal of the Brazilian Chemical Society; v. 26, n. 5, p. 837-850, MAY 2015.
• Web of Science Citations: 1

Abstract

Many natives from Amazon use poison secreted by the skin of some colorful frogs (Dendrobatidae) on the tips of their arrows to hunt. This habit has generated interest in the isolation of these toxins. Among the over 500 isolated alkaloids, the most important is undoubtedly (-)-epibatidine. First isolated in 1992, by Daly from Epipedobates tricolor, this compound is highly toxic (LD50 about 0.4 µg per mouse). Most remarkably, its non-opioid analgesic activity was found to be about 200 times stronger than morphine. Due to its scarcity, the limited availability of natural sources, and its intriguing biological activity, more than 100 synthetic routes have been developed since the epibatidine structure was assigned. This review presents the recent formal and total syntheses of epibatidine since the excellent review published in 2002 by Olivo et al.1 Mainly, this review is summarized by the method used to obtain the azabicyclic core. (AU)

• FAPESP's process: 09/00617-2 - Biocatalysis: the use of plant cells and lipases in organic synthesis - application on asymmetric synthesis of biologically active compounds
• Grantee: Alvaro Takeo Omori
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/18700-9 - Synthesis of substituted 7-azanorbornanes by intramolecular mannich reaction: application to asymmetric synthesis of epibatidine
• Grantee: Ronaldo Epifanio de Oliveira Filho
• Support Opportunities: Scholarships in Brazil - Master