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.

journal_name

Nat Prod Res

journal_title

Natural product research

authors

Passarella D,Barilli A,Efange SM,Elisabetsky E,Leal MB,Lesma G,Linck VM,Mash DC,Martinelli M,Peretto I,Silvani A,Danieli B

doi

10.1080/14786410500160645

subject

Has Abstract

pub_date

2006-07-10 00:00:00

pages

758-65

issue

8

eissn

1478-6419

issn

1478-6427

pii

L0X2Q5V68183W5U7

journal_volume

20

pub_type

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