Strategies for the Concise Syntheses of Complex Natural Products

复杂天然产物的简洁合成策略

• 批准号: 1564340
• 负责人: Christopher Vanderwal
• 金额: $ 45万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1564340&HistoricalAwards=false
• 关键词: Strategies; Concise; Syntheses; Complex; Natural

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Vanderwal of the Department of Chemistry at UC Irvine develop innovative designs for the assembly of structurally complex naturally occurring structures. The underlying theme of the work is the strategic use of inexpensive and readily available molecular building blocks to arrive at the complex architectures of the targeted natural products in as few chemical operations as possible. In so doing, existing synthetic methods are pushed to their limits by their use in very challenging contexts, and novel chemical reactivity is uncovered and utilized. The results of these studies positively impact any area of applied science that benefits from chemical synthesis, including pharmaceutical development, materials science, and more. This grant also supports outreach activities to middle school students from underserved communities to engage in scientific experiments on-campus, and simultaneously learn about the college experience. The intellectual merit of this proposal is the development of several strategies for the rapid buildup of the molecular architectures of four different types of complex natural products. The Himbert intramolecular arene/allene cycloaddition reaction and the resulting strain-driven rearrangement of the cycloadducts, transformations that have both previously been carefully investigated in these laboratories, are being leveraged in a concise synthesis of a small family of alkaloids. A combination of an arene-terminated cation-pi cyclization, a bioinspired A-ring cleavage, and a cycloaddition of a novel cumulene equivalent Diels-Alder dienophile set the stage for a rapid synthesis of a complex diterpenoid. An underutilized heterocycle annulation is leveraged to synthesize a structurally unique antibiotic alkaloid. Finally, either a concise and unusual but potentially biogenetically relevant route or a more conventional approach facilitate the first synthesis in an unusual family of complex alkaloids. The broader impacts of this work include the exceptional research training for undergraduate and graduate students. This grant also supports the UCI-LEAPS program that brings in local middle school students for day-long experiences in university chemistry and physics laboratories.

在这个由化学部化学合成计划资助的项目中，加州大学欧文分校化学系的Vanderwal教授开发了用于组装结构复杂的天然结构的创新设计。这项工作的基本主题是战略性地使用廉价且易于获得的分子构建模块，以尽可能少的化学操作来获得目标天然产品的复杂结构。在这样做的过程中，现有的合成方法通过在非常具有挑战性的环境中使用而被推向极限，并且发现和利用了新的化学反应性。这些研究的结果对任何受益于化学合成的应用科学领域产生了积极影响，包括药物开发，材料科学等。这项赠款还支持外展活动，以中学生从服务不足的社区从事校园内的科学实验，并同时了解大学的经验。 这一建议的智力价值是发展了几种策略，用于快速建立四种不同类型的复杂天然产物的分子结构。Himbert分子内芳烃/丙二烯环加成反应和由此产生的应变驱动的重排的环加合物，转换，这两个先前已经仔细研究在这些实验室，正在利用一个简洁的合成一个小家族的生物碱。芳烃封端的阳离子-π环化、生物启发的A环裂解和新颖的枯烯等价物狄尔斯-阿尔德亲二烯体的环加成的组合为复杂二萜类化合物的快速合成奠定了基础。利用未充分利用的杂环成环来合成结构独特的抗生素生物碱。最后，无论是一个简洁和不寻常的，但潜在的生物遗传学相关的路线或更传统的方法，促进第一个合成在一个不寻常的家庭复杂的生物碱。这项工作的更广泛的影响包括本科生和研究生的特殊研究培训。这笔赠款还支持UCI-LEAPS计划，该计划将当地中学生带到大学化学和物理实验室进行为期一天的体验。