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

Daniele 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)758-765
Number of pages8
JournalNatural Product Research
Volume20
Issue number8
DOIs
StatePublished - Jul 10 2006

Keywords

  • Antiwithdrawal effect
  • Ibogaine
  • Ibogaine analogs
  • Microwave-assisted reactions

ASJC Scopus subject areas

  • Molecular Medicine
  • Plant Science
  • Chemistry(all)
  • Biochemistry

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