Methodolgy For The Synthesis Of The Derivates Of Double Substituted Pyrrolidone Esters

Clausenamide, a kind of Pyrrolidone compounds, is isolated from aqueous extract of leaves of Clausena lansium. Bade on the pharmacological study, clausenamide could be used as liver protectant or nootropics. It can induce mouse liver cytochrome P450, have effects on aflatoxin B1-induced injury and the ability to reduce GPT level. Meanwhile it can improve the central cholinergic system, has a good nootropic, anti-oxidation, anti-Aβneurotoxicity, and inhibiting tau protein hyperphosphorylation effects. To improve pharmacokinetic properties and the dissolubility of clausenamide, some 3-subustitude and 3,7-disubstitude ester derivatives were synthesized, base on the principle of the optimization of the lead compound, such as molecular diversity, molecular similarity and molecular complementarity.Methodolgy for the modify of clausenamide has been studied thoroughly. Considered the structure features of the lead compound and the acylation ability of all kinds of acylating agents, as well as other factors, a suitable path to synthesis the target compounds is selected. Factors that effect the reaction conditions are also been discussed. All of the target compounds were characterized by means of elemental analysis, IR, 1H-NMR, MS.