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

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.     

The production ofJ/ψ in 200 GeV/A oxygen-uranium interactions

The dimuon production in 200 GeV/nucleon oxygen-uranium interactions is studied by the NA 38 Collaboration. The production ofJ/ψ, correlated with the transverse energyET, is investigated and compared to the continuum, as a function of the dimuon massM and transverse momentumPT. A value of 0.64±0.06 is found for the ratio (ψ/Continuum at highET)/(ψ/Continuum at lowET), from which theJ/ψ relative suppression can be extracted. This suppression is enhanced at lowPT.