Synthesis of a New Class of Antimalarial Cyclic Peroxide Derivatives

点击翻译按钮获取中文摘要

This research project was to synthesize a new class of antimalarial cyclic peroxide derivatives using manganese(III)-based oxidative radical cyclization which was reported by the head investigator.1. Catalytic autoxidation of a mixture of 4-piperidone-3-carboxylates and alkenes in the presence of manganese(III) acetate gave 2,3-dioxabicyclo[4.4.0]decane derivatives in high yields. Eighteen 2,3-dioxabicyclo[4.4.0]decanes could be obtained according to the catalytic reaction.2. A similar reaction of 4-hydroxy-2-quinolinones with alkenes did not give cyclic peroxides but bis(hydroperoxyalkyl)quinolinones in moderate to good yields.3. A similar reaction of 1,2-disubstituted pyrazolidine-3,5-diones with alkenes also gave bis(hydroperoxyalkyl)pyrazolidinediones in excellent yields. Fifteen new bis(hydroperoxyalkyl)pyrazolidinedione derivatives could be obtained in high based on the reaction.4. The manganese(III)-based catalytic autoxidation of 4-monosubstituted 1,2-diphenylpyrazolidine-3,5-diones was carried out in the absence of alkenes to give direct hydroperoxidation products in quantitative yields. A similar reaction of 5-monosubstituted barbituric acid derivatives also yielded 5-hydroperoxybarbituric acids in good yields.5. The structures of 2,3-dioxabicyclo[4.4.0]decanes, bis(hydroperoxyalkyl)quinolinones, bis(hydroperoxyalkyl)pyrazolidinediones, and 4-hydroperoxypyrazolidine-3,5-diones were determined by X-ray crystallography.6. Bis(hydroperoxyalkyl)pyrazolidinediones and 4-hydroperoxypyrazolidine-3,5-diones had a weak antimalarial activity.