SYNTHETIC STUDIES TOWARDS TAXOL AND RELATED COMPOUNDS

紫杉醇及相关化合物的综合研究

• 批准号: 2096359
• 负责人: YOSHITO KISHI
• 金额: $ 8.55万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2096359
• 关键词: aldehydes; alkaloids; analog; antineoplastics; biological products; catalyst; chemical models; chemical structure function; chromium; diterpenes; drug design /synthesis /production; nickel; paclitaxel; stereochemistry

The major objective of this research is to make significant contributions to organic chemistry and medicine through synthetic studies towards the taxane class of natural products, specifically focused on the antitumor alkaloid taxol. Our research efforts will be focused on the development of a practical, general, and flexible total synthesis of taxol for two purposes: (1) to secure a large scale supply of taxol or the most effective taxol analogue for clinical use and (2) to provide a wide variety of taxol analogues for structure/activity studies in order to identify the most effective taxol analogue. Experimentally, we plan to construct the ring B of taxol at the very late stage of synthesis by using the Ni(II)/Cr(Il)-mediated coupling reaction in a simultaneous or step-wise manner. Obvious advantages of this approach include a high degree of convergence and flexibility and a minimum number of steps required for the functional group manipulation after the key coupling reaction. By using a model system, we have demonstrated the feasibility of this approach.

这项研究的主要目的是使 通过合成研究对有机化学和医学的贡献 迈向紫杉烷类天然产品，特别关注 抗肿瘤生物碱紫杉醇。 我们的研究工作将集中于 开发实用，一般和灵活的总合成 紫杉醇出于两个目的：（1）确保大规模的紫杉醇供应或 用于临床使用的最有效的紫杉醇类似物，（2）提供 用于结构/活动研究的各种各样的紫杉醇类似物 确定最有效的紫杉醇类似物。 在实验上，我们计划 在合成的很晚阶段构建紫杉醇的环B 在同时或 逐步的方式。这种方法的明显优势包括高 收敛性和灵活性程度以及最小数量的步骤 键耦合后功能组操作所需 反应。 通过使用模型系统，我们已经证明了可行性 这种方法。