Synthetic Studies on the Gelsemium Alkaloids Based on the Biogenetic Speculation

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The genus Gelsemium contains more than forty of indole and oxindole alkaloids having various skeletal type. These alkaloids can be classified into five category based on the structural features and on the biogenetic speculation proposed by by us. Throughout the research project, We succeeded in the biomimetic synthesis of four different type of Gelsemium alkaloids.1. Sarpagine-type indole alkaloids : We succeeded in the synthesis of new Gelsemium alkaloids, koumidine and 19Z-anhydrovobasinediol, starting from ajmaline, which was corresponding chemically to the hypothetical biogenetic intermediate. The configuration of the ethylidene side chain in these alkaloids were also confirmed.2. Humantenine-type oxindole alkaloids : By the stereoselective transformation of 19Z-anhydrovobasinediol and gardnerine derivative using OsO_4 oxidation, the synthesis of N_a-desmethoxyrankinidine and N_a-desmethoxyhumantenirine, respectively, were accomplished. The absolute configuration of the humantenine … More -type alkaloids was first elucidated by this chemical correlation.3. Gelsedine-type oxindole alkaloids : Gelsedine-type compounds features the lack of C-21 carbon from usual monoterpenoid indole alkaloids. We first prepared hypothetical biogenetic intermediates, D-norsarpagine compounds from ajmaline and attempted their transformation into the oxindole derivatives. But, thus obtained oxindole had the opposite configuration at C7 spiro-position. Then, along to the alternative biogenetic speculation, we synthesized N_a-desmethoxygelsemicine by the removal of C-21 carbon from humantenine-type type oxindole alkaloids.4. Koumine : Koumine would generate biogenetically by the bond connection between the C7 adn C20 in the sarpagine-type indole alkaloid. We proved chemically this hypothesis by the palladium-catalyzed intramolecular coupling reaction between the C7 and C20 in 18-acetoxyanhydrovobasinediol.In conclusion, we succeeded in the synthesis of sarpagine-type, humantenine-type, gelsedine-type, and koumine along to our biogenetic proposal. The synthesis of one of the principal Gelsemium alkaloids, gelsemine, and development of the general procedure for the synthesis of N_a-methoxy oxindole derivatives still remain. Less