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.

在化学综合计划（SYN）方案的支持下，印第安纳大学（IU-Bloomington）的David Williams教授将开发新的方法和策略，以建造复杂的生物活性分子。 这些概念很重要，原因有两个。 有必要为分子复杂性的组装设计更有效的程序，同时找到环境良性的试剂和反应。 其次，需要扩大结构化学的限制，以鉴定生物学上活跃的新脚手架，既是化学生物学的工具，又是潜在的HIT，甚至是药物化学的铅化合物。 将探索多步合成途径，以制备生物活性天然产物。该项目尤其集中在反应性化合物的金属催化环化反应上，作为一种可能导致单个反应中两个或多个环形成的特征。 该项目的教育方面旨在广泛地发展学生作为有机化学领域的问题解决者。 该实验室经验的大多数毕业生都用于制药和生物技术行业。 社会福利将包括在研究的各个方面招募和参与代表性不足的个人和妇女。 该研究项目的本科参与者也将提供夏季研究机会。该研究项目旨在为合成方法，尤其是环化反应策略奠定新的基础。 应变的环丙烷和环丙烯的过渡金属催化反应将作为合成复杂的，生物活性天然产物的新途径的关键元素。 所提出的活动有望提高有关取代环丙烷的合成的知识，并有效地将这些反应性构建块纳入复杂的分子体系结构中。 这些研究还将检查小环金属赛在环化过程中形成更稳定的pi-ailyl金属中间体的倾向。 项目目标旨在设计一个反应级联，以分子内[3+2]和[2+2+1]环化结束。 还计划通过检查催化剂及其配体施加的电子和空间因子的反应范围和立体选择性。 提出了新的合成策略，用于有效地建造三环氰和fusicoccanes，以及完成daphnicyclidinA的合成。该项目是印第安纳大学化学系（科学，技术，工程和数学）承诺的重要组成部分，重点是对女性和不足的人进行访问。 通过与盟军学科的科学家进行计划的合作，预计将产生更广泛的科学影响，包括生物学，动物科学，神经科学和医学。 总体而言，该项目旨在推进基本的有机化学方法论和战略，并为现代合成化学方面的学生培训提供卓越的平台。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估来评估的值得支持的。

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