Excellence in Research: Stereoselective Synthesis of Spiro-Oxepin Core: Toward the Total Synthesis of Psammaplysin Natural Product and Analogues for Biological Study

该项目由化学合成计划和促进竞争性研究的既定计划（EPSCoR）共同资助。它支持了Ashton Hamme教授的研究，他正在开发一种合成途径，以合成一类称为“psammaplysins”的天然分子及其类似物。总的来说，它们的生物活性将由该项目的联合首席研究员Clement Yedjou教授进行研究。天然产物的全合成是化学生物学研究中不可缺少的动态工具，也是一项具有挑战性和令人兴奋的研究。Hamme博士专注于开发一种“功能基团”的合成方法，这种“功能基团”在psammaplysins中发现，其合成和生物学评价几乎没有研究过。在这个项目中，Hamme博士使用一种循序渐进的断键和成键方法，利用可以作为催化剂的有机分子合成天然产物的核心。这些催化剂选择性地构建目标分子中具有挑战性的结构。进一步转化该单元可导致psammaplysin及其类似物的全合成。杰克逊州立大学（JSU）是历史上第七大黑人学院和大学（HBCU），也是密西西比州唯一的城市大学，拥有吸引和留住少数民族学生的独特机会。JSU鼓励代表性不足的少数族裔学生通过基于研究的教育项目从事STEM职业。该项目的成果与世界级的科学出版物、专业报告和参加区域/国家会议有关，学生可以通过网络和全球化扩展他们的职业培训和机会。在这项提议中，Hamme教授正在开发一种对映选择性途径，以达到在sammaplysins中发现的高度取代和不寻常的spirooxepin核心。正在开发的路线涉及立体选择性，串联烷基化/迈克尔加成反应序列，由各种奎宁和手性尿素，硫脲和方酰胺有机催化剂催化。这些催化剂被设计用来激活酮，从而启动反应序列。这项工作正在解决一个合成挑战，研究的生物成分探讨了这些分子的结构和生物活性之间的关系。参与该项目的本科生、研究生和STEM学生正在接受化学和生物学界面的培训和挑战，扩大他们接触不同领域的机会，并在学术界、政府实验室、制药工业和国防研究实验室获得机会。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project is jointly funded by the Chemical Synthesis Program and the Established Program to Stimulate Competitive Research (EPSCoR). It supports the research of Professor Ashton Hamme who is developing a synthetic route to a class of naturally occurring molecules called the "psammaplysins" and their analogues. Collectively, their biological activity will be studied by the co-Principal Investigator in this project, Professor Clement Yedjou. The total synthesis of natural products is an indispensable and dynamic tool in chemical biology research and is often challenging and exciting. Dr. Hamme is focusing on developing methods for the synthesis of a "functional group" found in the psammaplysins whose synthesis and biological evaluation are scarcely studied. In this project, Dr. Hamme is using a stepwise bond-breaking and bond-making approach to synthesize the core of the natural product using organic molecules that can act as catalysts. These catalysts are selectively constructing the challenging architecture found in these target molecules. Further transformation of this unit leads to the total synthesis of psammaplysin and its analogues. Jackson State University (JSU), the seventh largest among Historically Black Colleges and Universities (HBCU) and the only urban University in Mississippi, has a unique opportunity to attract and retain minority students in the educational pipeline. Underrepresented minority students are encouraged to engage in STEM careers through a research-based educational program at JSU. The outcome of the project is associated with world-class scientific publications, professional presentations, and participation in regional/national meetings, where students extend their career training and opportunities via networking and globalization.In this proposal, Professor Hamme is developing an enantioselective route to the highly substituted and unusual spiro-oxepin core found in the psammaplysins. The route being developed involves a stereoselective, tandem ketalization/Michael addition reaction sequence catalyzed by various quinine and chiral urea, thiourea, and squaramide organocatalysts. These catalysts are designed to activate the ketone thereby initiating the reaction sequence. This work is solving a synthetic challenge, and the biological component of the study probes the relationship between the structure and biological activity of these molecules. The undergraduate, graduate, and STEM students involved in this project are being trained and confronted with challenges at the interface of chemistry and biology, broadening their exposure to diverse fields and to opportunities in academia, government laboratories, pharmaceutical industries, and defense research laboratories.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.