ASYMMETRIC SYNTHESIS OF IONOPHORE & MACROLIDE ANTIBIOTIC

离子载体的不对称合成

• 批准号: 3282904
• 负责人: David A Evans
• 金额: $ 28.61万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3282904
• 关键词: antibiotics; antineoplastic antibiotics; antineoplastics; boronic acids; catalyst; drug design /synthesis /production; ion transport; ionophores; iridium; ketones; macrolide antibiotics; oligomycins; rare earth element; reduction; stereochemistry

The objectives of this proposed research are to make creative contributions to the total synthesis of naturally occurring substances possessing clinically significant biological activity. The present grant will continue to address the development of new stereoselective reactions and the application of this methodology to the asymmetric synthesis of ionophore and macrolide antibiotics and antineoplastic agents. The methodological studies dealing with new reaction discovery will emphasize the development of new reactions for controlling the stereochemical course of chemical processes. In the present study we will continue to focus our attention on "directable" chemical processes. These studies will focus on the continued development of an iridium-catalyzed directable hydroboration process, the development of a directable Meerwein-Ponndorff-Verley reduction based on samarium diiodide, and the application of intramolecular variants of the Tishchenko reaction for long-range directed reductions of ketones. The targets for total synthesis will include the development of asymmetric syntheses of the antineoplastic agents bryostatin, calyculin, macbecin, and herbimycin, the ionophore antibiotic lonomycin, and the oligomycin macrolide rutamycin.

这项拟议的研究的目标是使创造性 对天然物质总合成的贡献 具有临床意义的生物活性的。目前的赠款 将继续致力于开发新的立体选择性反应 以及该方法学在不对称合成中的应用 离子载体、大环内酯类抗生素和抗肿瘤药物。这个 处理新反应发现的方法学研究将强调 控制立体化学的新反应的发展 化学过程的课程。在本研究中，我们将继续 把我们的注意力集中在“可指导的”化学过程上。这些研究 将专注于继续开发一种以铱为催化剂的 可定向氢化工艺，可定向发展的 基于二碘化钐的Meerwein-Ponndorff-Verley还原，以及 Tishchenko反应的分子内变体在生物合成中的应用 酮的长程定向还原。 全合成的目标将包括开发 抗肿瘤药物Bryostatin，Calyculin， Macbecin和Herbimycin，离子载体抗生素lonomycin，以及 寡霉素、大环内酯类、鲁他霉素。