Molecular design to develop a novel tool for the elucidation of the function of glutamates

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Chiral sulfinylmaleimides, a typical sulfinylethene-type dienophiles, react with various dienes to give the corresponding cycloadducts in highly diastereoselective manner. The aim of this research project is to develop a new tool to clarify the fucntion and the molecular understanding of glutamates in the human brain. For that purpose the chiral synthesis of glutamate and phosphoglutamate derivatives having the bicyclo [2.2.1] heptane ring system have been investigated and the following results were obtained.1) The chiral synthesis of glutamate and phosphoglutamate derivatives having the bicyclo [2.2.1] heptane ring system : Asymmetric Diels-Alder reaction of the sulfinylmaleimides with cyclopentadiene afforded the single diastereomeric cycloadduct. The reduction of the cycloadduct followed by the N-acyliminium cyanation afforded the key intermediate for the glutamate synthesis. After several conversion process, the objective glutamate derivatives were obtained as dimethylammonium salt … More , whose bioassay show the NMDA antagonistic activity. These glutamate could be good lead compounds for further molecular design. The acyliminium addition of phosphorus nucleophiles afforded the corresponding phosphorus esters. The hydrolytic cleavage of the phosphorus esters was very difficult to give the objective phosphoglutamate derivatives.2) Asymmetric Diels-Alder Cycloaddition of the Sulfinylethenes under Ultrahigh Pressure : In order to extend the scope of the above Diels-Alder reaction, the reaction of various sulfinylethenes with low-reactive dienes have been systematically studied. It was turned out that under the ultrahigh pressure conidition the low reactive dienes react with sulfinylethenes to give the corresponding cycloadducts highly diastereoselectively. The steric course of the reaction turned out to be the same as that was established under atmospheric pressure. So, the ultrahigh pressure methodology is quite useful for the molecular design of the glutamate receptor antagonists (or agonists) having the bicyclo [2.2.1] -heptane and-octane system. Less