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
Published: Natural Product Research
Date: 10 July 2006
Category:Chemistry, Synthesis, Neurochemistry, Medicine, Pharmacology
Tags:analogs
Comments:
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.