17310-94-0Relevant articles and documents
Retro-diels-alder reaction: Possible involvement in the metabolic activation of 7-oxabicyclo[2.2.1]hepta-2(3),5(6)-diene-2,3-dicarboxylates and a phosphonate analog
Mahajna, Mahmoud,Quistad, Gary B.,Casida, John E.
, p. 241 - 246 (1996)
A discontinuous structure-activity relationship signaled a change in mode of action and led to the discovery of a possible novel metabolic activation mechanism. The toxicity of the herbicide endothal (exo,exo-7- oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid) to mice (ip LD50 = 14 mg/kg) is attributed to the inhibition of protein phosphatase 2A (PP2A) at the cantharidin binding site. The potency is reduced by the introduction of a 2,3- or 5,6-double bond. Surprisingly, high toxicity (ip LD50's = 15-50 mg/kg) is restored in oxabicyclohepta-2(3),5(6)-dienes substituted in the 2- and 3-positions with bis(methyl carboxylate), bis(ethyl carboxylate), and diethyl phosphonate/ethyl carboxylate, whereas the dicarboxylic acid, bis(tert-butyl carboxylate), and bis(dimethyl phosphonate) are inactive. The diene adducts do not inhibit the cantharidin binding site of PP2A. Two observations provided an alternative working hypothesis that the active but not the inactive diene adducts are protoxicants: GC analyses revealed that selected bicyclic dienes readily undergo thermal dissociation by retro- Diels-Alder reactions to liberate disubstituted acetylenes; the liberated acetylenes have mouse ip LD50's of 8-25 mg/kg. Apparent exceptions to this hypothesis are that bicyclic dienes with bis(tert-butyl carboxylate) and bis(dimethyl phosphonate) substituents are not toxic, yet their corresponding acetylenes are quite toxic. These apparent anomalies are resolved by finding that only the toxic bicyclic dienes readily react with albumin and 4- nitrobenzenethiol and that their low-toxicity analogs are much less reactive. Albumin can be replaced by hemoglobin but not by myoglobin or chymotrypsin in reaction with a bicyclic diene indicating the importance of the free thiol group. Diethyl oxabicycloheptadienedicarboxylate readily reacts with GSH to give two products, which are also formed from the corresponding acetylene, identified as the cis and trans isomers of the GSH-acetylene conjugate. This is the first proposal, to our knowledge, that a retro-Diels-Alder-type reaction is involved in the metabolic activation of a toxicant.
New bifunctional substrates for copper-catalyzed asymmetric conjugate addition reactions with trialkylaluminium
Ladjel, Chehla,Fuchs, Nicolas,Zhao, Jinkai,Bernardinelli, Gerald,Alexakis, Alexandre
scheme or table, p. 4949 - 4955 (2010/01/18)
Trialfylaluminium reagents have been found to undergo a copper-catalyzed asymmetric conjugate addition (ACA) reaction with oxabicyclo[2.2.1]hepta-2,5- diene-2,3-dicarboxylates with the simultaneous creation of two stereocenters. Different types of ligands
Synthese organique sous champ microondes: Premier exemple d'activation specifique en phase homogene
Berlan,Giboreau,Lefeuvre,Marchand
, p. 2363 - 2366 (2007/10/02)
The rate of several Diels-Alder reactions under conventional or microwave heating are compared at the same bulk temperature. This afford the first evidence for a specific activating effect of microwaves under homogeneous conditions.
