NATURAL PRODUCT SYNTHESIS VIA IMINIUM YLIDE & NITRILIUM

目标将是开发改进的化学合成方法，用于 生物活性天然产物及其结构类似物。这些 合成注定要依赖于概念上的新奇环化 之前的事。具体地说，我们建议开发对映体选择性合成 对于依赖于恶唑啉的生物碱石榴碱和倍他西汀 叶立德1，3-偶极环加成反应。水仙生物碱 倍他西汀已显示出显著的治疗潜力。这 该物质具有显著的抗艾氏腹水癌活性。 老鼠。更重要的是，个人的治疗活动 标准药物阿霉素和环磷酰胺治疗上述疾病 通过辅助性治疗，肿瘤显著增加 普雷他西汀。此外，黄连蛋白的独立抑制作用 倍他西汀对阿霉素作用下细胞蛋白质合成的影响 已经在KB细胞培养中得到证实。值得注意的是，倍他西汀有 已被证明能提高小鼠的存活率和存活时间 刘易斯肺癌在低水平给药时超过几个 几天。此外，治疗效果的标准有多种 药物(如环磷酰胺、放线菌素D、5-氟尿嘧啶、甲氨蝶呤、 6-硫代鸟嘌呤和长春新碱)。种植型Lewis肺癌 协同或相加地增加了与 普雷他西汀。 生物活性生物碱丹参碱和丹参碱的简明合成 提出了eburnamonine的新概念。通往这些天然产品的预定路线 将利用一种新的方法来实现酰基氮离子环化反应 这是我们最近开发的。我们预测，这部小说意味着 有效地构建可变环大小的杂环将产生 在生物碱合成领域产生了重大影响。

The objectives will be to develop improved chemical systheses for biologically active natural products and their structural analogs. These syntheses are destined to rely on conceptually novel annulation precedures. Specifically, we propose to develop enantioselective syntheses for the alkaloids dendrobine and pretazettine which rely on oxazolinium ylide 1,3-dipolar cycloaddition reactions. The narcissus alkaloid pretazettine has exhibited remarkable therapeutic potential. This substance has shown marked activity against Ehrlich ascites carcinoma in mice. More importantly, the therapeutic activity of the individual standard drugs adriamycin, and cycloposphamide against the forementioned carcinoma was increased tremendously by the adjuvant therapy with pretazettine. In addition, the independent inhibitory action of pretazettine on cellular protein synthesis in the presence of adriamycin has been demonstrated in KB-cell cultures. Significantly, pretazettine has been revealed to increase both the survival rate and survival time of mice with Lewis lung carcinoma when administered at low levels over several days. In addition, the therapeutic effectiveness of a variety of standard drugs (e.g. cyclophosphamide, actinomycin D, 5-fluorouracil, methotrexate, 6-thioguanine, and vincristine) against i.p. implanted Lewis lung carcinoma was increased synergistically or additively when coadministered with pretazettine. Concise syntheses for the biologically active alkaloids erythraline and eburnamonine are proposed. The intended routes to these natural products will utilize a new procedure for effecting acylnitrilium ion cyclizations which we have recently developed. We predict that this novel means for efficiently constructing heterocycles of variable ring size will create a significant impact in the area of alkaloid synthesis.