Asymmetric Reactions by the Use of Pyridinophane with Planar Chirality

使用具有平面手性的吡啶芬进行的不对称反应

• 批准号: 08640756
• 负责人: ASAMI Masatoshi
• 金额: $ 1.47万
• 依托单位: Yokohama National University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08640756/
• 关键词: nicotinamide-adenine; pyridinophane; planar chirality; flash vacuum pyrolysis; optical resolution; asymmetric reduction; ピリドキサミン; ニコチンアデニンジヌクレオチド; 面性不斉; 熱分解反応; ジチアファン; 脱硫反応

Nicotinamide-adenine dinucleotide (NAD) is an important coenzyme involved in many oxidation and reduction reactions in biological system. Parapyridinophane derivatives having planar chirality was designed as model compounds of the coenzyme to investigate a highly stereoselective organic reactions. A synthesis and optical resolution of the pyridinophane and its use in asymmetric reduction of ethyl benzoylformate was examined in this study.The synthesis of a parapyridinophane derivative, 8-ethoxycarbonyl[2]paracyclol[2] (2,5)-pyridinophane, was started from a coupling reaction of 2,5-bis (bromomethyl)-3-ethoxy-carbonylpyridine and 1,4-bis-(mercaptomethyl) benzene. The corresponding dithiaphane was obtained in 51% yield and it was then oxidized to the corresponding disulfone in 94% yield with m-chloroperbanzoic acid. The flash vacuum pyrolysis of the disulfone afforded the desired parapyridinophane derivative in 53% yield after detailed study of the reaction conditions of the pyrolysis. T … More hen the pyndinophane derivative was subjected to optical resolution and it was found that the resolution was achieved by HPLC using a chiral column to afford the desired optically active parapyridinophane, It was also separated as diastereomers after converting to amide with chiral 1-phenylethylamine. The parapyridinophanes were then derived to the coresponding dihydropyridine derivatives by N-methylation with methyl iodide followed by reduction with sodium dithionite. Reduction of ethyl benzoylformate was examined by using these dihydropyridine derivatives. However, the reaction did not proceeded and the starting material was recovered. To examine the reason that the reaction did not take place, a synthesis of another dihydropyridinophane with less strained structure was carried out. 8-Ethoxycarbonyl [3] paracyclo [3] (2,5)-pyridinophane was obtained in racemic form by using the similar reaction scheme. The optical resoluton and derivatization to the corresponding dihydropyridine derivative will be examined in due course.Although the asymmetric reduction of ethyl benzoylformate has not yet been realized using NADH model compounds of parapyridinophane, the synthetic route for para-pyridinophane derivative was established by this study. The synthetic utility of these compounds will be reported in the future. Less

烟酰胺 - 腺苷二核苷酸（NAD）是与生物系统中许多氧化和还原反应有关的重要辅酶。具有平面性手性的甲吡二酚衍生物被设计为辅酶的模型化合物，以研究高度立体选择性的有机反应。在这项研究中检查了吡啶二酚的合成和光学分辨率及其在不对称还原中的使用。 （溴甲基）-3-乙氧基 - carbonylpyridine和1,4-双（近甲基甲基）苯。以51％的产率获得了相应的二硫烷，然后将其用M-氯氯苯甲酸氧化为94％的二硫酮。在详细研究热解的反应条件后，二硫酮的闪光真空热解提供了53％的产量。 t…更多的吡喃烷烷衍生物进行了光学分辨率，发现该分辨率是通过HPLC使用手性色谱柱实现的，可以提供所需的光学活性甲帕吡啶二酚，它也被作为非对映异构体分离为非对映异构体后用呼射1-苯胺1-苯基甲胺转化为酰胺。然后，伴吡啶寄生虫通过用甲基碘化物N-甲基化，然后用二硫代硫酸钠降低，将甲状腺素衍生物衍生在二氢吡啶衍生物中。通过使用这些二氢吡啶衍生物检查乙基苯甲酰甲酸酯的还原。但是，反应没有进行，起始材料被回收。为了检查反应没有发生的原因，进行了另一种二氢吡啶二氨基烷的合成，其结构较少。 8-乙氧基钙[3] Paracyclo [3]（2,5） - 吡啶二酚是通过使用类似的反应方案以消极形式获得的。将在适当的时候检查光学分辨率和对相应的二氢吡啶衍生物的衍生化。这些化合物的合成效用将在未来报告。较少的