ASYMMETRIC SYNTHESIS OF IONOPHORE/MACROLIDE ANTIBIOTICS

离子载体/大环内酯类抗生素的不对称合成

• 批准号: 2176981
• 负责人: David A Evans
• 金额: $ 29.6万
• 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/2176981
• 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意 对天然物质的总合成的贡献 具有临床上重要的生物学活性。 目前的赠款 将继续解决新的立体选择反应的发展 以及这种方法在不对称合成中的应用 离子载体和大环内酯类抗生素以及抗肿瘤剂。 这 涉及新反应发现的方法学研究将强调 开发用于控制立体化学的新反应 化学过程的过程。 在本研究中，我们将继续 将注意力集中在“可导向”的化学过程上。 这些研究 将重点放在虹膜催化的持续发展上 引导水合过程，开发 Meerwein-Ponndorff-Verley基于samarium diiodide的减少， Tishchenko反应的分子内变体的应用 长期定向酮的降低。 总合成的目标将包括开发 抗肿瘤剂的非对称合成曲霉素，钙化蛋白，钙蛋白酶 Macbecin和Herbimycin，离子载体抗生素lonomycin，以及 寡霉素大霉素丁霉素。