NEW METHODS FOR ALKALOID SYNTHESIS

在此提出的研究的主要目标是发展 一种新的、通用的合成议定书，用于准备各种 具有重要药用价值的生物碱。靶结构、吡咯烷或 3-吡咯啉熔合到另一个环上，氮气位于桥头 地位，在自然界中广泛流传。为了准备这个亚基， 分子内L，一个氧化物在二烯上的3-偶极环加成反应 建议。然后，生成的乙烯基三唑啉将转化为 3-吡咯啉的光解反应。叠氮二烯的制备简便性 前体以及快速构建生物碱的机会 具有适当立体中心的环形系统实现了这一点 潜在的非常重要的。这种方法的灵活性将是 通过合成一些具有生物医学意义的化合物来证明 化合物(吡咯里西丁生物碱、苦马豆素、斯莱夫拉明、麻黄毒素、 葛根素)。在这些合成的框架内，有几个未探索的 乙烯基三氮唑和乙烯基氮杂环丙烷的化学领域将是 地址。 作为一个共同的目标，一种合成光学纯的新方法 提出了将杂多酸作为手性起始物质的方法。 上述生物碱合成的原料。一定程度上的融合 杂环(如L、3-二氧杂环戊酮、4H-1，3-二恶英-4-酮)至 手性助剂将为转移提供刚性框架 碳-碳键形成反应中的立体化学信息。在……里面 这样，氨基酸及其衍生物的α-羟基酸和β-羟基酸 都会做好准备。

The principal objective of the research proposed herein is the development of a new and general synthetic protocol for the prepatation of a variety of medicinally important alkaloids. The target structure, a pyrrolidine or 3-pyrroline fused to another ring with the nitrogen at the bridgehead position, is widely spread in nature. To prepare this subunit, intramolecular l,3-dipolar cycloaddition of an axide onto a diene is proposed. The resultant vinyl triazoline will then be transformed into a 3-pyrroline by photolysis. The ease of preparation of the azido diene precursors as well as the opportunity for rapid construction of alkaloidal ring systems with appropriate stereocenter incorporation makes this work potentially very significant. The flexibility of this method will be demonstrated by the synthesis of a number of biomedically significant compounds (pyrrolizidine alkaloids, swainsonine, slaframine, pumiliotoxins, gephyrotxin). Within the framework of these syntheses, several unexplored areas in the chemistry of vinyl triazolines and vinyl aziridines will be addressed. As a concurrent goal, a new method for the synthesis of optically pure heteroacids is proposed, which will be utilized as chiral starting materials for the above alkaloid syntheses. The fusion of certain heterocycles (l,3-dioxolan-4-ones, 4H-1,3-dioxin-4-ones, for example) to chiral auxilliaries will provide rigid frameworks for the transfer of stereochemical information during carbon-carbon bond forming reactions. In this way, Alpha- and Beta-hydroxyacids of amino acids and their derivatives will be prepared.