NEW METHODS FOR ALKALOID SYNTHESIS

本文提出的研究的主要目标是开发 一种新的和通用的合成方案，用于制备各种 医药上重要的生物碱。 目标结构，吡咯烷或 3-在桥头与氮稠合到另一个环上的吡咯啉 位置，在自然界中广泛传播。 为了制备该亚基， 将一种氧化物分子内1，3-偶极环加成到二烯上， 提出了 然后将所得乙烯基三唑啉转化为 3-通过光解的吡咯啉。 叠氮基二烯的制备容易性 以及快速建设的机会， 具有适当立构中心结合的环系统使得该工作 可能非常重要。 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（吡咯里西啶生物碱，苦马豆素，slaframine，pumiliotoxins， gephyrotxin）。 在这些综合的框架内，一些未探索的 乙烯基三唑啉和乙烯基氮杂环丙烷的化学领域将是 处理。 作为一个共同的目标，一种新的方法来合成光学纯的 杂酸，这将被用作手性起始 用于上述生物碱合成的材料。 某些元素的融合 杂环化合物（例如，1，3-二氧戊环-4-酮，4 H-1，3-二氧杂环己烯-4-酮）， 手性助剂将提供刚性框架， 在碳-碳键形成反应期间的立体化学信息。 在 这样，氨基酸的α-和β-羟基酸及其衍生物 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.