ALKALOID SYNTHESIS USING ORGANORHODIUM CHEMISTRY

这项研究计划的目标是全面综合 石蒜科生物碱家族的几个成员， 灯盏花素和倍他西汀及其生物碱的合成 石冠菊。我们的计划围绕着进一步发展 有机铑化学在有机合成中的应用 展示一种新的铑的威力和多功能性 最新的烯烃官能化反应 在我们的实验室里发现的。 石蒜科生物碱具有广泛的生物学活性。 活动。班上的一些成员已经被展示了 具有显著的抗菌和抗真菌活性。Crinafoline 和倍他西汀已被证明可以减少癌症的生长 肿瘤细胞。倍他西汀也显示出抗病毒活性。 HAEMANTITY通过以下途径抑制真核细胞蛋白质合成 抑制多肽键的形成步骤。止痛活性 加兰他明被归因于它与 吗啡骨架。 我们合成石蒜科生物碱的方法将是 最初的重点是蛋白质合成抑制剂的合成， 被认为是一种生物合成的 苏丹定的前体；以及抗病毒生物碱， 普雷他西汀。赤霉胺和奎宁都是从 亚洲红豆杉。它们的结构是由 光谱手段和化学转化。普雷他西汀 从包括哈曼瑟斯在内的各种来源分离出来 Natalsis和H.harrisiana在合成路线中的应用 石蒜科其他生物活性生物碱的合成 是有计划的。 石杉内酯是倍半萜内酯的代表 生物碱，由兰花物种金银花产生， 其骨骼结构和药物学性质相似 强效惊厥印防己毒素。装饰性的 Dendrobine最初是从中国兰花中分离出来的 用来制作中药“金石虎”。Dendrobine已经 已被证明对解毒巴比妥酸盐中毒有效 它还表明，β-丙氨酸和牛磺酸具有拮抗作用 属性。 石蒜科生物碱和石竹碱都提供了理想的 我们促进了调查新罗兰范围的目标 烯烃官能化反应序列。

The goals of this research proposal are the total synthesis of several members of the Amaryllidaceae alkaloid family, crinine, haemanthidine and pretazettine and the synthesis of the alkaloid dendrobine. Our plan centers around the further development of organorhodium chemistry in organic synthesis and the demonstration of the power and versatility of a new rhodium based olefin functionalization reaction which was recently discovered in our laboratories. The Amaryllidaceae alkaloids display a wide range of biological activity. Some members of the class have been shown to exhibit pronounced anti-bacterial and anti-fungal activity. Crinafoline and pretazettine have been shown to reduce the growth of cancer tumor cells. Pretazettine also shows antiviral activity. HAEMANthidine halts protein synthesis in eukaryotic cells by inhibiting the peptide bond formation step. The analgesic activity of galanthamine has been attributed to its resemblance to the morphine skeleton. Our approach to the synthesis of the Amaryllidaceae alkaloids will initially focus on the syntheses of the protein synthesis inhibitor, haemanthidine; crinine, which is thought to be a biosynthetic precursor to haemanthidine; and the antiviral alkaloid, pretazettine. Haemanthidine and crinine were both isolated from Crinum asiaticum. Their structures were determined by spectroscopic means and chemical transformations. Pretazettine was isolated from a variety of sources including Haemanthus natalensis and H. harrisiana application of our synthetic route to the synthesis of other biologically active Amaryllidaceae alkaloids is planned. Dendrobine is representative of a group of sesquiterpene lactone alkaloids, produced by the orchid species Dendrobium nobile, whose skeletal structure and pharmalogical properties are similar to those of the potent convulsant picrotoxin. The ornamental Chinese orchid from which Dendrobine was isolated was originally used to make the Chinese drug "Chin-Shih-Hu". Dendrobine has been shown to be effective in antidoting barbituate intoxication and it also shows beta-alanine and taurine antagonizing properties. Both the Amaryllidaceae alkaloids and Dendrobine provide ideal targets for investigating the scope of our new rhodium promoted olefin functionalization reaction sequence.