SYNTHETIC STUDIES TOWARDS TAXOL AND RELATED COMPOUNDS

紫杉醇及相关化合物的综合研究

• 批准号: 3199607
• 负责人: YOSHITO KISHI
• 金额: $ 8.39万
• 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/3199607
• 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.

这项研究的主要目标是取得重大成果 通过综合研究对有机化学和医学做出贡献 面向紫杉烷类天然产物，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、通用、灵活的全合成 紫杉醇有两个目的：（1）确保紫杉醇的大规模供应或 临床使用最有效的紫杉醇类似物，并且（2）提供 用于结构/活性研究的各种紫杉醇类似物 以确定最有效的紫杉醇类似物。 我们计划通过实验 在合成的最后阶段构建紫杉醇的B环 使用 Ni(II)/Cr(II) 介导的偶联反应同时或 逐步的方式。这种方法的明显优点包括高 收敛性和灵活性的程度以及最少的步骤数 键耦合后进行官能团操作所需的 反应。 通过使用模型系统，我们证明了可行性 这种方法。