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

为了有效地构建目标分子，作者研究了一种新的合成方法的发展，特别是使用钯催化的环烯基化反应和一种新的串联电子转移反应的杂化技术。由于作者最近开发了钯催化环烯基化反应，因此本项目采用了C_<20>赤霉素合成的方案。C_<20>赤霉素（GA）的<20>CD环部分具有双环[3.2.1]辛烷环体系，利用钯催化的环烯基化反应合成C_赤霉素（GA）的CD环体系非常方便。有了适当功能化的CD环部分，作者决定利用分子内的反电子需求Diels-Alder反应来构建C_赤霉素的AB环体系<20>。结果，上述杂交方案立体选择性地提供了GA_<12>、GA_<111>和GA_。 ...更多信息 作者<112>接着考察了新的串联反应的发展，并找出了一次合成双环[2.2.2]辛烷环体系的高烯丙基-高烯丙基自由基重排过程。树胶阿魏酸是已知的二萜类化合物，作为最强的植物激素之一，并且在CD环部分具有双环[2.2.2]辛烷环单元。作者将高烯丙基-高烯丙基自由基重排反应应用于植物激素的制备中，首次实现了高烯丙基-高烯丙基自由基重排反应与分子内Diels-Alder反应相结合的（±）-甲基树胶阿魏酸酯的全合成，并发展了1-氮杂二烯炔的杂Diels-Alder反应，用于构建马匹碱型生物碱的基本碳骨架。由于马匹辛具有很强的生物活性，人们报道了许多合成方法。作者以上述杂Diels-Alder反应为关键步骤，完成了马匹辛的六步形式合成。作为该方法的应用，通过钯催化的Sonogashira反应和分子内杂Diels-Alder反应的杂交，实现了3步合成洛托宁A，从而成功地开发了几种新的杂交技术，以合成多种具有生物活性的天然产物。少

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