Cyclization Strategies and Methodologies Toward the Synthesis of Complex Natural Products

复杂天然产物合成的环化策略和方法

• 批准号: 2102587
• 负责人: David Williams
• 金额: $ 50万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2102587&HistoricalAwards=false
• 关键词: Cyclization; Strategies; Methodologies; Toward; Synthesis

With the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor David Williams of Indiana University (IU-Bloomington) will develop new methods and strategies for the construction of complex, bio-active molecules. These concepts are important for two principal reasons. There is a need to devise more efficient procedures for the assembly of molecular complexity while finding environmentally benign reagents and reactions. Secondly, there is need to expand the limits of structural chemistry to identify new scaffolds that are biologically active, both as a tools for chemical biology and as potential hit or even lead compounds for medicinal chemistry. Multi-step synthesis pathways will be explored for the preparation of bio-active natural products; this project is especially focused on metal-catalyzed cyclization reactions of reactive compounds as a feature that may lead to the formation of two or more rings in a single reaction. Educational aspects of this project are geared to broadly develop students as problem-solvers in the field of organic chemistry. Most of the graduates from this laboratory experience are employed in the pharmaceutical and biotechnology industries. Societal benefits will include the recruitment and participation of under-represented individuals and women in all aspects of the research. Summer research opportunities will also be available for undergraduate participants in this research project. This research project seeks to forge new ground in synthetic methodology and particularly in strategies for cyclization reactions. Transition metal-catalyzed reactions of strained cyclopropanes and cyclopropenes will be explored as a key element in the design of new pathways for the synthesis of complex, bio-active natural products. The proposed activities are expected to advance knowledge regarding the synthesis of substituted cyclopropanes and the effective incorporation of these reactive building blocks into complex molecular architectures. These investigations will also examine the propensity for reorganization of small ring metallacycles to form more stable pi-allyl metal intermediates in cyclization processes. Project objectives seek to devise a reaction cascade concluding with intramolecular [3+2] and [2+2+1] cyclizations. Studies are also planned on reaction scope and stereoselectivity through the examination of electronic and steric factors imposed by the catalyst and its ligands. New synthesis strategies are proposed for the efficient construction of tricyclic cyathanes and fusicoccanes, as well as for completion of the synthesis of daphnicyclidin A. The project is a significant component of the Indiana University Department of Chemistry STEM (Science, Technology, Engineering and Mathematics) commitment with an emphasis on access for women and underrepresented individuals through the IU ACS Bridging Program. Broader scientific impacts are expected through planned collaborations with scientists in allied disciplines including biology, animal sciences, neuroscience and medicine. Overall, this project aims to advance fundamental organic chemistry methodology and strategy and to provide a superior platform for student training in modern synthetic chemistry.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.

在化学系化学合成(SYN)计划的支持下，印第安纳大学(IU-Bloomington)的大卫·威廉姆斯教授将开发构建复杂的生物活性分子的新方法和策略。这些概念之所以重要，主要有两个原因。有必要设计更有效的程序来组装分子复杂性，同时寻找环境友好的试剂和反应。其次，有必要扩大结构化学的范围，以确定具有生物活性的新支架，既可以作为化学生物学的工具，也可以作为潜在的重要化合物甚至是药物化学的先导化合物。将探索制备生物活性天然产物的多步合成途径；该项目特别侧重于金属催化的活性化合物的环化反应，这是一个可能导致在一个反应中形成两个或更多环的特征。这个项目的教育方面旨在广泛地培养学生在有机化学领域解决问题的能力。这一实验室经验的毕业生大多受雇于制药和生物技术行业。社会福利将包括招募和参与任职人数不足的个人和妇女参与研究的各个方面。这个研究项目的本科生也有暑期研究的机会。这一研究项目寻求在合成方法学，特别是环化反应策略方面建立新的基础。过渡金属催化的应变环丙烷和环丙烯反应将作为设计合成复杂、生物活性天然产物的新途径的关键因素。预计拟议的活动将促进有关取代环丙烷的合成以及将这些活性构建块有效地结合到复杂分子结构中的知识。这些研究还将考察环化过程中小环金属环重组以形成更稳定的pi-烯丙基金属中间体的倾向。项目目标试图设计一个以分子内[3+2]和[2+2+1]环化结束的反应级联反应。还计划通过检查催化剂及其配体施加的电子和空间因素来研究反应范围和立体选择性。该项目是印第安纳大学化学系STEM(科学、技术、工程和数学)承诺的重要组成部分，重点是妇女和代表性不足的个人通过IUACS桥接计划获得机会。通过与生物学、动物科学、神经科学和医学等相关学科的科学家进行有计划的合作，预计将产生更广泛的科学影响。总体而言，该项目旨在推进基础有机化学方法和战略，并为学生在现代合成化学方面的培训提供一个优越的平台。该奖项反映了NSF的法定使命，并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。

项目成果

IBX Oxidations for the Synthesis of Substituted 2H-Pyrans

用于合成取代 2H-吡喃的 IBX 氧化

• DOI: 10.3987/com-20-s(k)69
• 发表时间: 2021
• 期刊: HETEROCYCLES
• 影响因子: 0.6
• 作者: R. Williams, David;A. Bawel, Seth;Haddadpour, Nazanin;Maier, Sarah
• 通讯作者: Maier, Sarah