STRUCTURAL STUDIES OF ENOLATES FOR ORGANIC SYNTHESIS

有机合成烯醇化物的结构研究

• 批准号: 3071840
• 负责人: Paul G. Williard
• 金额: $ 5.62万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3071840
• 关键词: antineoplastic antibiotics; antineoplastics; drug design /synthesis /production; enolate; macrolide antibiotics; plant extracts; stereochemistry; terpenes; tetracyclines

The principal aim of the research program set forth in this application is to improve the synthetic methodology currently used to synthesize compounds with anticancer activity. In particular the stereoselectivity of the synthetic reactions is of major concern. Some examples of active compounds are the terpenoids; phyllanthoside, which has demonstrated activity against the NCI murine B16 melanoma as well as some life extension against the PS leukemia cell line, and taxol, which has demonstrated activity against the B16 melanoma as well as the colon CX-1 adenocarcinoma xenograft and the MX-1 mammary carcinoma xenograft. While the source of these compounds is from plant extracts, a suitable synthetic route would be preferable| The work outlined herein will greatly assist with the ongoing development of synthetic routes to the compounds mentioned above as well as offer the possibility for improvement in the synthetic routes to the tetracyclane antitumor antibiotics in the daunomycin family and the novel spirocyclic antitumor compound fredericamycin. The overall, long range goal of this work remains to explain the reactivity of the most common and useful organic nucleophiles and to predict with certainty the stereochemistry of the important synthetic reactions in which these species are used. The substrates under study are the primary reagents in the construction of architecturally complex organic molecules such as the terpenoid tumor promoters and inhibitors and especially the macrolide antibiotics. Positive results from this investigation will permit a more rational choice of reagents for the asymmetric synthesis of the physiologically active organic molecules.

本研究计划的主要目标 应用是为了改进目前的合成方法 用于合成具有抗癌活性的化合物。 在 特别是合成反应的立体选择性是 主要关注点。 活性化合物的一些例子是 萜类化合物；叶花苷，已证明具有活性 对抗 NCI 小鼠 B16 黑色素瘤以及一些生命 抗 PS 白血病细胞系的延伸和紫杉醇， 已证明具有抗 B16 黑色素瘤活性 结肠CX-1腺癌异种移植物和MX-1乳腺 癌异种移植。 虽然这些化合物的来源是 从植物提取物中，合适的合成路线是 优选| 本文概述的工作将极大地帮助 持续开发化合物的合成路线 上面提到的以及提供改进的可能性 四环烷类抗肿瘤抗生素的合成路线 道诺霉素家族和新型螺环抗肿瘤药物 复方弗雷德里霉素。 这项工作的总体、长期目标仍然是解释 最常见和有用的有机亲核试剂的反应性 并准确地预测其立体化学 使用这些物质的重要合成反应。 所研究的底物是主要试剂 构建结构复杂的有机分子，例如 萜类肿瘤促进剂和抑制剂，特别是 大环内酯类抗生素。 这项调查的积极结果将 允许更合理地选择不对称试剂 生理活性有机分子的合成。