Strategy-Guided Syntheses of Complex Natural Products

在国家科学基金会化学部化学合成(SYN)计划的支持下，加州大学欧文分校(UCI)化学系的Christopher D.Vanderwal教授正在开发组装结构复杂的自然分子的创新方法。这项工作的基本主题是战略性地使用现成的分子构件，以尽可能少的化学操作达到目标天然产品的复杂结构。在这样做的过程中，现有的化学方法将由于在非常具有挑战性的环境中的使用而被推向极限，预计将发现快速建立复杂分子结构的新策略。这些研究的结果将对许多受益于化学合成的应用科学领域产生积极影响，包括药物开发和材料科学。这笔赠款还将允许面向服务不足社区的中学生开展外展活动，让他们在校园内进行科学实验，同时了解大学经历。Vanderwal小组将进一步参与当地社区大学生的指导工作，使他们能够拥有他们的第一次实验室研究经验。这些研究的核心在于开发几种策略，以快速组装几种有趣的天然产品的复杂分子结构。首先，其他化学家通过长序列合成的复杂多环生物碱Arcutinine将通过一个简洁和高度收敛的设计来定位，该设计寻求通过一个短的多键形成序列将两个同样复杂的片段结合在一起。其次，二氢-β-琼脂呋喃-一组500多个立体化学复杂的高度含氧的萜类化合物具有许多有趣的生物学特性-将从高度氧化的B环开始以高效的方式组装，其本身将通过立体选择性苯还原或不对称Diels-Alder化学的新应用来获得。最后，通过一种新颖的分子内环加成反应来合成高效、选择性的抗胰腺癌药物阿亮氨胺，这也将推动新的反应性的发展。这项工作的更广泛影响包括为本科生和研究生提供特殊的研究培训。这笔赠款还支持UCI-LEAPS计划和UC-SCC计划，UCI-LEAPS计划吸引当地中学生在大学化学和物理实验室进行为期一天的体验，UC-SCC计划支持当地社区大学生在加州大学洛杉矶分校的化学实验室实习。该奖项反映了NSF的法定使命，通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Synthesis (SYN) Program in the Chemistry Division of NSF, Professor Christopher D. Vanderwal of the Department of Chemistry at UC Irvine (UCI) is developing innovative approaches for the assembly of structurally complex naturally occurring molecules. The underlying theme of the work is the strategic use of 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 chemical methods will be pushed to their limits by their use in very challenging contexts, and new strategies for rapidly building complicated molecular architectures are expected to be uncovered. The results of these studies will positively impact the many areas of applied science that benefit from chemical synthesis, including pharmaceutical development and materials science. This grant will also permit outreach activities to middle school students from underserved communities to engage in scientific experiments on-campus, and simultaneously learn about the college experience. The Vanderwal group will further engage in the mentorship of local community college students and enable them to have their first laboratory research experiences. The core of these research studies lie in the development of several strategies for the rapid assembly of the complex molecular architectures of several interesting natural products. First, the complex polycyclic alkaloid arcutinidine, which has been synthesized via lengthy sequences by other chemists, will be targeted via a concise and highly convergent design that seeks to unite two equally complex pieces via a short multiple-bond-forming sequence. Second, the dihydro-beta-agarofurans—a group of over 500 stereochemically complex, highly oxygenated terpenoids with many interesting biological properties—will be assembled in an efficient manner starting from a highly oxidized B-ring, which itself will be accessed via novel applications of either stereoselective benzene reductions or asymmetric Diels–Alder chemistry. Finally, the potent and selective anti-pancreatic-tumor agent aleutianamine will be synthesized by a novel intramolecular cycloaddition reaction, which will also drive the development of new reactivity. 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, and the UC-SCC program that supports the internship of local community college students in chemistry labs at UCI.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.