TOTAL SYNTHESIS OF POLYCYCLIC NATURAL PRODUCTS

多环天然产物的全合成

• 批准号: 6636030
• 负责人: CLAYTON H HEATHCOCK
• 金额: $ 25.34万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6636030
• 关键词: alkaloids; antineoplastics; biological products; carbopolycyclic compound; chemical structure function; chemical synthesis; cyclization; drug design /synthesis /production; enzyme inhibitors; isoprenoid; molecular rearrangement

DESCRIPTION: (Principal Investigator's Abstract) Although chemists have become rather adept at constructing small amounts of very complicated molecules, we generally cannot prepare most desired organic compounds in an efficient , practical, and cost-effective manner. Our general inability to conceive and execute practical laboratory syntheses constitutes a frailty of our science. It is the long-term goal of this research to address this deficiency by exploring new strategies for the laboratory synthesis of complex organic structures. The compounds to be synthesized are molecules of Nature-alkaloids, carbohydrates, isoprenoids, and acetogenins. The intent is not just to make compounds, but to do it in a way that will teach us something new about the architectural aspect of molecule-building. Specific synthetic targets are cylindramide, discorhabdin D, sarain A, croomine, cephalostatin 12, euthyroideones A-C, arnoamines A-B, halichlorine, pinnaic acid, and tauropinnaic acid. The fundamental significance of the kind of research being carried out in this project is the improvement of our synthetic abilities. It is for this reason that we identify novel organic structures and strive to discover non-obvious, efficient methods to assemble them from commercially-available building blocks. Our ultimate goal as synthetic chemists is to be able to synthesize any desired organic molecule, no matter how complex, in a manner that would be ameanable to commercial production. However, many of the targets we have chosen have intrinsic biological importance, and our synthetic research might have immediate practical importance. Among these targets are discorhabdin D, cephalostatin 12, and halichlorine, compounds so rare that insufficient material is available for full scale in vivo evaluation. Through total synthesis we hope to remedy this problem.

描述：（首席研究员的摘要）尽管化学家已经成为 我们非常擅长构建少量非常复杂的分子， 通常不能有效地制备大多数所需的有机化合物， 实用且具有成本效益的方式。我们普遍无法怀孕 执行实际的实验室合成是我们科学的一个弱点。它 本研究的长期目标是通过探索来解决这一缺陷 复杂有机结构实验室合成的新策略。这 要合成的化合物是天然分子——生物碱、碳水化合物、 类异戊二烯和 acetogenins。其目的不仅仅是制造化合物，而是 以一种能够教会我们一些关于建筑方面的新知识的方式来做 分子构建。具体的合成目标是 cylindramide、discorhabdin D、sarain A、克鲁明、头孢他汀 12、甲状腺素 A-C、阿诺胺 A-B、 卤氯、羽肉酸和牛磺羽酸。 本次研究的根本意义 项目是我们综合能力的提高。正是因为这个原因 我们识别新颖的有机结构并努力发现非显而易见的， 从商业上可用的构建块组装它们的有效方法。 作为合成化学家，我们的最终目标是能够合成任何想要的化合物 有机分子，无论多么复杂，以一种易于理解的方式 商业化生产。然而，我们选择的许多目标 内在的生物学重要性，我们的合成研究可能具有 具有直接的实际意义。这些目标包括discorhabdin D、 头孢他汀 12 和卤氯，这些化合物非常稀有，不足以满足需要 材料可用于全面的体内评估。通过总计 我们希望通过综合来解决这个问题。