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

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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