Synthesis of a New Class of Antimalarial Cyclic Peroxide Derivatives

一类新型抗疟环状过氧化物衍生物的合成

基本信息

批准号：
13640539
负责人：
NISHINO Hiroshi
金额：
$ 2.3万
依托单位：
Kumamoto University (2002)Kyushu University (2001)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

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.

该研究项目是使用基于锰（III）的氧化自由基环化来合成新的一类新的抗疟疾过氧化衍生物，该氧化剂衍生物由锰（III）。在乙酸锰（III）存在下4哌啶酮-3-羧酸盐和烯烃混合物的催化自氧化得到了高产量的2,3-二甲烷[4.4.0]脱烷衍生物。可以根据催化反应获得十八个2,3-二甲状腺素[4.4.0] decan。 4-羟基-2- Quinolinones与烷烃的类似反应没有给出环状过氧化物，而是中等至良好产量的BIS（Hydroperoxyalkyl）喹诺酮类酮。3。 1,2二取代的吡唑啉-3,5-二离子与烷烃的类似反应也使双（氢过氧基烷基）吡唑烷基化二酮具有出色的产率。根据反应，可以在高中获得15个新的BIS（氢过氧）吡唑烷基化衍生物。4。基于锰（III）的基于锰的1,2-二苯基吡唑啉-3,5-二酮的催化自氧化是在没有烷烃的情况下进行定量产率的直接氢过氧产物的。 5单叠取代的巴比妥酸衍生物的类似反应也产生了5-氢氧化甲贝比瑞克酸，其产量良好。5。由X射线晶体术确定了2,3-二氧化碳[4.4.0] decanes，bis（hydroxyalkyl）喹诺酮类酮，二甲烷基甲醇烯酮，二吡唑烷基）的吡唑啉酮和4-羟恶作羟唑啉-3,5-二酮的结构。 BIS（氢过氧基烷基）吡唑烷二酮和4-羟基氧甲唑啉-3,5-二酮的抗疟疾活性较弱。