Selective H/D Exchanged Reaction To Synthesize Deuterated Carboxylic Acid With 8?Aminoquinoline As The Directing Group In Heavy Water And Anti-Epileptic Activity Evaluation Of Deuterated Sodium Valproate

Deuterated compounds are a series of chemicals which are substituted by D atom.For a long time,deuterated compounds have been widely used in pharmaceutical analysis,organic chemistry study and many other fields due to their specific physicochemical properties.Besides,deuterated compounds also are being found their potencial value in pharmaceutical chemistry field.Some deuterated pharmaceutical drugs are able to prevent themselvies from metabolic inactivation,reduce the amount of toxic metabolites and stabilize their stereo configuration compared with undeuterated drugs.In this way,selective deuterated reaction to the specific site of pharmacurtical drugs to improving relevant effects has been developed and applied in pharmacuetical design.Accordingly,in order to synthesize desired deuterated compounds,the requirement of exploiting novel deuterated reactions especailly selective deuterated reactions is ever-increasing.The first part of this article contains the review of deuterated compounds and deuterated reactions recently,and the second part combines the utilization of 8-aminoquinoline as directing group to achieve C-H bond functionalization and palladium-catalyzed deuterated reactions in homogeneous system proposing selective H/D exchanged reaction to synthesis deuterated carboxylic acid with 8?aminoquinoline as the directing group in heavy water.With this reaction condition,we synthesized seven ortho-d-N-8-quinolinylaromaticamides with different substituent group on benzene ring and eight ?-d-N-8-quinolinylfattyacidamides.Meanwhile we selected five of them to hydrolyze getting deuterated carboxylic acid ultimately including ?-d-alproic acid whosesynthetic process was amplified into gram-scale.All the D incorperation of products was 75-100% except 2e and 2m.We also proposed a possible mechanism.Sodium valproate is a kind of widely used anti-epileptic drug.Considering of that ?-position is a significant spot of metabolization,we conceived it was possible that ?-d-sodium valproate could improve the efficacy property.The third part of this article contians the study of anti-epileptic activity evaluation of deuterated sodium valproate in PTZ mice model.We made a comparison with sodium valproate and ?-d-sodium valproate in these 4 aspcets: the acute epilepsy incubation period,the number of acute seizures,the rank of acute seizures and the death rate.The results showed that each of them had their own advantages.All in all,we can not make a conclution that which one is much more better in anti-epileptic activity.