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.

Passarella, D.; Barilli, A.; Efange, S. M. N.; Elisabetsky, E.; Leal, M. B.; Lesma, G.; Linck, V. M.; Mash, D. C.; Martinelli, M.; Peretto, I.; Silvani, A.; Danieli, B.

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.

ALDER; ETHYL acrylate; DOPAMINE; HYDROGENATION; ACRYLATES

Natural Product Research, 2006, Vol 20, Issue 8, p758

1478-6419

Academic Journal

10.1080/14786410500160645