Fungicidal and Neurotoxic Marine Natural Products

杀菌和神经毒性海洋天然产品

• 批准号: 6836441
• 负责人: JON Douglas RAINIER
• 金额: $ 22.43万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836441
• 关键词: Fungicidal; Neurotoxic; Marine; Natural; Products

EXCEED THE SPACE PROVIDED. Natural products that have been isolated from the marine environment show promise as _harmacological agents. However, because of the supply problems associated with their isolation, a thorough evaluation of their properties requires their chemical synthesis. This proposal describes the chemical synthesis of three biologically important marine natural products. The first of these is gambierol, a marine ladder toxin associated with ciguatera poisoning. The second is armatol A, a polycyclic ether that has demonstrated interesting cytotoxicity in preliminary testing. The third is halichondrin B, a potent anticancer agent that has been recommended for preclinical trials in spite of its short supply. Gambierol, armatol A, and halichondrin B have in common a fused polycyclic ether skeleton. This proposal outlines the chemical synthesis of these agents centered around carbon-glycosides. As carbon-glycosides have been demonstrated to be important, not only in synthetic chemistry, but also in medicinal chemistry, we believe that this strategy might have broad implications. In addition, by coupling our carbon-glycoside forming chemistry with efficient annulation protocols, we believe that we will be able to efficiently generate polycyclic ethers including the natural products listed above. Furthermore, these efforts will undoubtedly lead to the generation of a number of interesting and biologically important analogs whose properties will be evaluated. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。从海洋环境中分离出来的天然产物有希望成为药物制剂。然而，由于与它们的分离相关的供应问题，对其性质的彻底评估需要它们的化学合成。该提案描述了三种具有生物重要性的海洋天然产物的化学合成。第一种是甘比洛尔，一种与雪卡毒有关的海洋梯形毒素。第二种是armatol A，这是一种多环醚，在初步测试中显示出有趣的细胞毒性。第三种是软海绵素B，这是一种有效的抗癌药物，尽管供应短缺，但仍被推荐进行临床前试验。甘比尔醇、armatol A和软海绵素B共同具有稠合的多环醚骨架。该提案概述了以碳糖苷为中心的这些试剂的化学合成。由于碳苷已被证明是重要的，不仅在合成化学，而且在药物化学，我们相信，这一战略可能具有广泛的影响。此外，通过将我们的碳糖苷形成化学与有效的成环方案相结合，我们相信我们将能够有效地产生多环醚，包括上面列出的天然产物。此外，这些努力无疑将导致产生一些有趣的和生物学上重要的类似物，其性质将被评估。性能现场=