TOTAL SYNTHESIS OF POLYCYCLIC NATURAL PRODUCTS

多环天然产物的全合成

• 批准号: 6519450
• 负责人: CLAYTON H HEATHCOCK
• 金额: $ 25.35万
• 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/6519450
• 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：（主要研究者的摘要）尽管化学家已经成为 我们善于构建少量非常复杂的分子，我们 通常无法在有效的，有效的， 实用，具有成本效益的方式。我们一般无法受孕和 执行实践实验室合成构成了我们科学的脆弱。它 这是这项研究的长期目标，即通过探索来解决这一缺陷 实验室合成复杂有机结构的新策略。这 要合成的化合物是自然 - 类卵生的分子，碳水化合物， 类异丙素和乙酰基蛋白。目的不仅是制造化合物，而且是 这样做的方式将教会我们有关建筑方面的新知识 分子建造。特定的合成目标是cylindramide，Discorhabdin D，Sarain A，Croomine，Cephalostatin 12，呼quhroideones A-C，Arnoamines A-B， 甲基氯，甲状酸和牛珠酸。 在此进行的研究的基本意义 项目是我们合成能力的提高。出于这个原因 我们确定了新颖的有机结构，并努力发现非明显的， 从商业上可用的构建块中组装它们的有效方法。 我们作为合成化学家的最终目标是能够综合任何所需的 有机分子，无论多么复杂，都可以美不合理 商业生产。但是，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 直接实际的重要性。这些目标中有迪斯托拉希丁D， 头孢洛替汀12和卤化氯酸酯的化合物如此罕见，以至于不足 材料可用于体内评估。通过总计 综合我们希望解决这个问题。