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Synthetic Studies on the Gelsemium Alkaloids Based on the Biogenetic Speculation

基于生物遗传学推测的钩吻生物碱的合成研究

基本信息

批准号：
01470136
负责人：
SAKAI Shin-ichiro
金额：
$ 4.1万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01470136/
关键词：
Gelsemium Indole Alkaloids Biomimetic Synthesis 生合成模擬反応化学変換反応

项目摘要

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

钩吻属含有四十多种具有不同骨架类型的吲哚和羟吲哚生物碱。根据结构特征和我们提出的生物发生推测，这些生物碱可分为五类。在整个研究过程中，我们成功仿生合成了四种不同类型的钩吻生物碱。 1． Sarpagine型吲哚生物碱：我们以ajmaline为原料，成功合成了新的钩吻生物碱、koumidine和19Z-anHydrovobasinediol，它在化学上与假设的生物中间体相对应。这些生物碱的亚乙基侧链构型也得到了证实。 2．人天宁型羟吲哚生物碱：通过OsO_4氧化对19Z-脱水伏巴辛二醇和加德纳林衍生物进行立体选择性转化，分别合成了N_a-去甲氧基兰尼定和N_a-去甲氧基人天宁。人藤碱型生物碱的绝对构型首先通过这种化学关联性得到阐明。 3． Gelsedine 型羟吲哚生物碱：Gelsedine 型化合物的特点是缺少普通单萜吲哚生物碱中的 C-21 碳。我们首先从阿马林制备了假设的生物中间体，D-去甲沙帕嗪化合物，并尝试将其转化为羟吲哚衍生物。但是，由此获得的羟吲哚在C7螺位具有相反的构型。然后，根据另一种生物发生学推测，我们通过从人天宁型羟吲哚生物碱中去除C-21碳，合成了N_a-去甲氧基凝胶半胺。 4． Koumine ： Koumine 将通过沙帕吉碱型吲哚生物碱中的 C7 和 C20 之间的键连接生物生成。我们通过钯催化18-乙酰氧基脱水伏巴辛二醇中C7和C20之间的分子内偶联反应，从化学上证明了这一假设。总之，我们根据我们的生物遗传学建议，成功合成了沙帕津型、人替宁型、格西定型和古曼碱。主要钩吻生物碱之一钩吻碱的合成以及合成 N_a-甲氧基羟吲哚衍生物的一般程序的开发仍然存在。较少的