Synthetic Studies on the Gelsemium Alkaloids Based on the Biogenetic Speculation

Gelsemium属含有40多种吲哚和氧吲哚生物碱，具有不同的骨骼类型。根据生物碱的结构特征和我们提出的生物成因推测，这些生物碱可分为五类。在整个研究项目中，我们成功地对四种不同类型的Gelsemium生物碱进行了仿生合成。sarpagine型吲哚类生物碱：我们成功地合成了新的Gelsemium类生物碱、koumidine和19z - anhydrovbasinediol，这与假设的生物成因中间体在化学上是相对应的。这些生物碱中乙基侧链的构型也得到了证实。人藤碱型氧吲哚类生物碱：用OsO_4氧化将19z -无氢巴辛二醇和栀子碱衍生物进行立体选择性转化，分别合成了n_a -去甲氧基rankinidine和n_a -去甲氧基人藤碱。这种化学相关性首次阐明了更多类型生物碱的绝对构型。格尔斯丁型氧吲哚生物碱：格尔斯丁型化合物的特点是缺乏通常的单萜类吲哚生物碱的碳-21。我们首先从ajmaline中制备了假设的生物遗传中间体d -去甲萘啶化合物，并尝试将其转化为oxindole衍生物。但是，由此得到的氧吲哚在C7螺旋位上具有相反的构型。然后，根据替代生物遗传学的推测，我们通过从人嘌呤型氧吲哚生物碱中去除C-21碳合成了n_a -去甲氧基凝胶半氨酸。Koumine: Koumine是由sarpagine型吲哚生物碱中C7和C20的键连接产生的。我们用钯催化的18-乙酰氧基氢巴辛二醇中C7和C20的分子内偶联反应从化学上证明了这一假设。综上所述，我们成功合成了sarpagine型、humantenine型、gelsedine型和koumine型，符合我们的生物遗传学建议。gelsemum主要生物碱之一gelsemine的合成和n_a -甲氧基氧吲哚衍生物的一般合成方法的开发仍在继续。少

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