Nature-inspired indolyl-2-azabicyclo[2.2.2]oct-7-ene derivatives as promising agents for the attenuation of withdrawal symptoms: synthesis of 20-desethyl-20-hydroxymethyl-11-demethoxyibogaine.

Abstract

Microwave assisted Diels-Alder cycloaddition of 5-Br-N-benzylpyridinone (2) with methyl acrylate is described to gain an easy access to 7-bromo-2-benzyl-3-oxo-2-aza-5 or 6-carbomethoxy bicyclo[2.2.2]oct-7-enes (3)-(6). The preparation of the ibogaine analogue 20-desethyl-(20-endo)-hydroxymethyl-11-demethoxyibogaine (17) is described by stereoselective hydrogenation of the C(7)-C(8) double bond. Biological evaluation showed an interesting in vitro binding profile toward dopamine transporter, serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14). The simplification of the ibogaine structure appears as a promising approach toward the design of compounds that could reduce the withdrawal symptoms.

• Authors: D Passarella, A Barilli, S M N Efange, E Elisabetsky, M B Leal, G Lesma, V M Linck, D C Mash, M Martinelli, I Peretto, A Silvani, B Danieli
• Journal: Natural product research (Nat Prod Res) Vol. 20 Issue 8 Pg. 758-65 (Jul 10 2006) ISSN: 1478-6419 [Print] England
• PMID: 16753910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 20-desethyl-20-hydroxymethyl-11-demethoxyibogaine
• Ibogaine

Topics

• Animals
• Ibogaine (analogs & derivatives, chemical synthesis, therapeutic use)
• Male
• Mice
• Molecular Structure
• Substance Withdrawal Syndrome (drug therapy)