50472-10-1Relevant articles and documents
Silver salt effects on an asymmetric Heck reaction. Catalytic asymmetric total synthesis of (+)-xestoquinone
Miyazaki, Futoshi,Uotsu, Koichiro,Shibasaki, Masakatsu
, p. 13073 - 13078 (1998)
An enantioselective total synthesis of (+)-xestoquinone has been achieved using a cascade-type asymmetric Heck reaction (in up to 63% ee and 39% chemical yield (66% conversion yield)) of the aryl bromide derivative(4). The use of a larger amount of silver
1-Aminomethylbenzocycloalkanes: Conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists
McLean, Thomas H.,Parrish, Jason C.,Braden, Michael R.,Marona-Lewicka, Danuta,Gallardo-Godoy, Alejandra,Nichols, David E.
, p. 5794 - 5803 (2007/10/03)
A series of conformationally restricted analogues of the hallucinogenic phenethylamine 1 (2,5-dimethoxy-4-bromophenethylamine, 2C-B) was synthesized to test several hypotheses concerning the bioactive conformation of phenethylamine ligands upon binding to the 5-HT2A receptor. These benzocycloalkane analogues were assayed for their receptor binding affinity and ability to activate downstream signaling pathways, and one exceptional compound was selected for testing in an in vivo drug discrimination model of hallucinogenesis. All compounds were examined in silico by virtual docking into a homology model of the 5-HT2A receptor. On the basis of these docking experiments, it was predicted that the R enantiomer of benzocyclobutene analogue 2 would be the most potent. Subsequent chemical resolution and X-ray crystallography confirmed this prediction, as (R)-2 proved to be equipotent to LSD in rats trained to discriminate LSD from saline. Thus, we propose that the conformation of 2 mimics the active binding conformation of the more flexible phenethylamine type hallucinogens. In addition, (R)-2 is one of the most potent and selective compounds yet discovered in the in vivo drug discrimination assay. Further, 2 was found to be a functionally selective agonist at the 5-HT 2A receptor, having 65-fold greater potency in stimulating phosphoinositide turnover than in producing arachidonic acid release. If hallucinogenic effects are correlated with arachidonic acid production, such functionally selective 5-HT2A receptor agonists may lack the intoxicating properties of hallucinogens such as LSD.
3,6-DIMETHOXYBENZOCYCLOBUTENONE: A REAGENT FOR QUINONE SYNTHESIS
Azadi-Ardakani, Manouchehr,Wallace, Timothy W.
, p. 5939 - 5952 (2007/10/02)
3,6-Dimethoxybenzocyclobutenone 4 is prepared in four efficient steps from 2,5-dimethoxybenzoic acid 8.The derived benzocyclobutenol 13 undergoes electrocyclic ring opening at 110-115 deg C to give the hydroxy-o-quinone dimethide 21, which reacts with dienophiles to give 5,8-dimethoxy-1,2,3,4-tetrahydro-1-naphthol derivatives stereoselectively.Since the ketone 4 can be functionalised at C-5 using electrophiles and at C-2 via homolytic bromation, the ring opening and cycloaddition sequence offers a flexible route to linear fused hydroquinone and quinone derivatives.In model studies, the benzocyclobutenol derivative 48 underwent thermal electrocyclic ring opening and intramolecular cycloaddition to give 49, while the analogous reaction with 52 failed due to adverse steric effects during the cycloaddition step.In photochemical experiments, attempts to generate the silyl ether 57 by in situ silylation of the dienol 55 and to prepare the benzocyclobutenol 62 via irradiation of the o-phthalaldehyde monoacetal 60 were unsuccessful.
