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DEVELOPMENT OF NOVEL SYNTHETIC METHODOLOGY BY A HYBRIDIZATION OF PALLADIUM-CATALYZED CYCLOALKENYLATION AND TANDEM ELECTRON TRANSFER REACTION

通过钯催化环烯基化和串联电子转移反应的杂化开发新的合成方法

基本信息

批准号：
11672097
负责人：
TOYOTA Masahiro
金额：
$ 2.24万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

In order to construct efficiently the target molecules, the author has investigated the development of a novel synthetic methodology, especially using a hybridization technique of the palladium-catalyzed cycloalkenylation reaction and a novel tandem electron transfer reaction. Since the author recently developed the palladium-catalyzed cycloalkenylation process, in this project, the author adopted the protocol for C_<20> gibberellin synthesis. It is extremely convenient to apply the palladium-catalyzed cycloalkenylation reaction to synthesize the CD ring system of C_<20> gibberellins (GA), because C_<20> gibberellins possess bicyclo[3.2.1]octane ring system at the CD ring part. With the suitably functionalized CD ring part in hand, the author next decided to use a reverse electron demand intramolecular Diels-Alder reaction for the construction of AB ring system of C_<20> gibberellins. As a result, the above hybridization protocol has stereoselectively provided GA_<12>, GA_<111>, and GA … More _<112>.The author has next examined the development of new tanden reaction, and found out homoallyl- homoallyl radical rearrangement process to synthsize bicyclo[2.2.2]octane ring system at one stroke. Gummiferolic acid is known diterpenoid as one of the strongest plant hormones, and has a bicyclo[2.2.2]octane ring unit at the CD ring part. The author applied the homoallyl-homoallyl radical rearrangement process to the plant hormone preparation, and the first total synthesis of (±)-methyl gummiferolate has been accomplished by a combination of homoallyl-homoallyl radical rearrangement reaction and intramolecular Diels-Alder reaction.Finally, the author has developed a hetero Diels-Alder reaction of 1-azadienyne for the construction of basic carbon framework of mappicine-type alkaloids. Since mappicine shows strong biological activities, many synthetic approaches have been reported. The author has accomplished a six-step formal synthesis of mappicine employing the above hetero Diels-Alder reaction as the key step. As an application of the method, 3-step synthesis of luotonin A has been achieved by a hybridization of palladium-catalyzed Sonogashira reaction and intramolecular hetero Diels-Alder reaction.In conclusion, the author has succeeded in developing several novel hybridization technologies in order to synthesize a wide variety of biologically active natural products. Less

为了高效地构建目标分子，作者研究了一种新的合成方法，特别是利用钯催化的环烯基化反应的杂交技术和一种新的串联电子转移反应。由于作者最近开发了钯催化环烯基化工艺，因此在本项目中，作者采用了C_<20>的赤霉素合成方案。由于C_<20>赤霉素在CD环部分具有双环[3.2.1]辛烷环体系，因此应用钯催化环烯化反应合成C_<20>赤霉素（GA）的CD环体系非常方便。在得到适当功能化的CD环部分后，作者决定采用分子内反电子需求diols - alder反应来构建C_<20 b>赤霉素的AB环体系。结果表明，上述杂交方案立体选择性地提供了GA_<12>、GA_<111>和GA_< 112>。接着考察了新链登反应的发展，发现了全烯丙基-全烯丙基自由基重排法，一次冲程合成双环[2.2.2]辛烷环体系。甘树醇酸被称为二萜类，是最强的植物激素之一，在CD环部分有一个双环[2.2.2]辛烷值环单元。作者将同丙烯基-同丙烯基自由基重排工艺应用于植物激素的制备，通过同丙烯基-同丙烯基自由基重排反应和分子内Diels-Alder反应的结合，首次合成了（±）-甘米酸甲酯。最后，作者开发了1-氮杂二烯的Diels-Alder反应，构建了mappicine型生物碱的碱性碳骨架。由于mappicine具有很强的生物活性，许多合成方法已被报道。作者以上述Diels-Alder反应为关键步骤，完成了六步正式合成mappicine。作为该方法的应用，通过钯催化的Sonogashira反应和分子内Diels-Alder反应的杂化，实现了三步法合成碘素A。综上所述，作者已经成功地开发了几种新的杂交技术，以合成各种具有生物活性的天然产物。少