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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13640539/
• 关键词: Heterocyclic compounds; Antimalarial activity; 1,2-Dioxan-3-ols; Manganese(III) acetate; Radical reaction; Catalytic oxidation; Hydroperoxide derivatives; Hydroperoxyalkylation; 有機過酸化物; 1,2-ジオキサン; 2-キノリノン類; ピラゾリジン-3,5-ジオン類; アルテミシニン; 酸化反応; ジヒ

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.

本课题是利用锰（III）基氧化自由基环化法合成一类新的抗疟药环过氧化物衍生物，由首席研究员报道。在（III）乙酸锰的存在下，4-哌酮-3-羧酸酯和烯烃的混合物催化自氧化得到高产的2,3-二恶沙环[4.4.0]癸烷衍生物。根据催化反应可得18个2,3-二恶二环[4.4.0]癸烷。4-羟基-2-喹啉酮与烯烃的类似反应没有得到环过氧化物，但得到双（氢过氧烷基）喹啉酮，产率中等至较高。1,2-二取代吡唑烷-3,5-二酮与烯烃的类似反应也得到了双（氢过氧烷基）吡唑烷二酮，收率很高。通过该反应，可以在较高的反应温度下得到15个新的双（氢过氧烷基）吡唑烷二酮衍生物。在不含烯烃的情况下，采用锰基催化4-单取代1,2-二苯基吡唑烷-3,5-二酮自氧化，得到了定量产率的直接氢过氧化产物。5-单取代巴比妥酸衍生物的类似反应也能产率很高的5-氢过氧巴比妥酸。用x射线晶体学测定了2,3-二恶沙环[4.4.0]十烷、双（氢过氧烷基）喹啉酮、双（氢过氧烷基）吡唑烷二酮和4-氢过氧吡唑烷-3,5-二酮的结构。双（氢过氧烷基）吡唑烷二酮和4-氢过氧基吡唑烷-3,5-二酮具有较弱的抗疟活性。

项目成果

Ryoukou Kumabe, Hiroshi Nishino, Kazu Kurosawa: "Catalytic Oxidation of 4-Piperidone-3-carboxylates with Manganese(III) Acetate in the Presence of Alkenes under Air"Tetrahedron Lett.. 42. 69-72 (2001)

Ryoukou Kumabe、Hiroshi Nishino、Kazu Kurosawa：“在空气中存在烯烃的情况下用乙酸锰 (III) 催化氧化 4-哌啶酮-3-羧酸盐”Tetrahedron Lett.. 42. 69-72 (2001)

Satoaki Onitsuka, Hiroshi Nishino*: "Synthesis of Polyfunctionalized Furans from 1-Aryl-2-pentene-1,4-diones"Tetrahedron. 59. 755-765 (2002)

Satoaki Onitsuka、Hiroshi Nishino*：“从 1-芳基-2-戊烯-1,4-二酮合成多官能化呋喃”四面体。

Ryoukou Kumabe, Hiroshi Nishino, Mikio Yasutake, Van-Ha Nguyen, and Kazu Kurosawa: "Catalytic Oxidation of 4-Piperidone-3-carboxylates with Manganese(III)Acetate in the Presence of 1,1-Disubstituted Alkenes"Tetrahedron Lett.. 42, (1). 69-72 (2001)

Ryoukou Kumabe、Hiroshi Nishino、Mikio Yasutake、Van-Ha Nguyen 和 Kazu Kurosawa：“在 1,1-二取代烯烃存在下用乙酸锰 (III) 催化氧化 4-哌啶酮-3-羧酸盐”Tetrahedron Lett..

西野 宏: "マンガン(III)に基づく酸化反応を利用した有機合成へ新展開"オレオサイエンス. 1. 491-501 (2001)

Hiroshi Nishino：“利用基于锰 (III) 的氧化反应进行有机合成的新进展”Oleoscience。1. 491-501 (2001)。

西野 宏: "マンガン(III)に基づく酸化反応を利用した有機合成への新展開"オレオサイエンス. 1. 491-501 (2001)

Hiroshi Nishino：“利用基于锰 (III) 的氧化反应进行有机合成的新进展”Oleoscience。1. 491-501 (2001)。