SYNTHESES OF MACROLIDES AND RELATED NATURAL PRODUCTS

大环内酯类及相关天然产物的合成

• 批准号: 3282568
• 负责人: FREDERICK E ZIEGLER
• 金额: $ 21.87万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-06-01 至 1993-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3282568
• 关键词: alkylation; antibacterial agents; antifungal agents; antineoplastics; drug design /synthesis /production; epoxides; ionophores; lenticular nucleus; macrolide antibiotics; pheromone; polyvinyls; stereoisomer; steroid glycoside aglycone

Polypropionate-derived natural products can function as antibiotics, ionophores and pheromones. The development of highly diastereoselective and enantioselective methods for the synthesis of these substances permits new techniques for analog synthesis and the advancement of the study of organic reaction mechanisms. Using Claisen rearrangements and palladium- mediated alkylations developed during the present granting period, efforts currently underway will be continued to test the efficacy of this new methodology in the synthesis of several physiologically-active substances. Two antibiotics, elaiophylin, in particular its physiologically- active aglycones, and protomycinolide IV, will be the subjects of synthetic studies that will test our method for polypropionate synthesis and carbon-carbon bond macrocyclization. In the area of ionophores, synthetic studies on calcimycin and X-14885-A, important ion transport agents in biological systems, will be conducted. The denticulatins are marine polypropionate natural products that are structurally related to putative biogenetic precursors of the antimicrobial diemenesins. Synthetic efforts directed toward their synthesis will aid in the study of the mechanism of their formation. The anti-cholesteremic agent, heptelidic acid, provides an opportunity to study the mechanism of intramolecular palladium- mediated alkylations of vinyl epoxides and to prove the absolute configuration of this substance by synthesis. All of these projects are currently under investigation.

聚丙酸衍生的天然产品可以作为 抗生素、离子载体和信息素。的发展。 高度非对映选择性和对映体选择性方法 这些物质的合成使类似物的新技术成为可能 有机反应的合成及其研究进展 机制。使用克莱森重排和钯- 在本授权书期间发生的调解烷基化反应 在此期间，目前正在进行的努力将继续测试 这种新方法在几个化合物的合成中的有效性 生理活性物质。 两种抗生素，弹力素，特别是它的生理学- 活性苷元和原霉素内酯IV将是 将测试我们的聚丙酸酯方法的合成研究 合成和碳-碳键大环化。在该地区 离子载体，钙霉素和X-14885-A的合成研究， 生物系统中重要的离子传输剂将是 指挥。 细菌素是海洋聚丙酸酯的天然产物， 在结构上与推测的生物发生前体有关 抗菌双烯菌素。综合努力，以期 它们的合成将有助于研究它们的作用机制。 队形。 抗胆固醇药七烷酸提供了一种 研究分子内钯的机理的机会- 环氧乙烯基烷基化反应及其绝对值的证明 通过合成这种物质的构型。 所有这些项目目前都在调查中。