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已建立的激励竞争性研究计划(EPSCoR)共同资助。它支持阿什顿·哈姆教授的研究，他正在开发一种合成路线，以获得一类自然产生的分子，即“沙棘毒素”及其类似物。总体来说，它们的生物活性将由该项目的联合首席研究员Clement Yedjou教授研究。天然产物的全合成是化学生物学研究中不可缺少的、充满活力的工具，常常是具有挑战性和激动人心的。Hamme博士正专注于开发合成方法，以合成在Psammaplysins中发现的“官能团”，其合成和生物学评价很少被研究。在这个项目中，哈姆博士正在使用一种循序渐进的断键和成键方法，利用可以充当催化剂的有机分子来合成天然产品的核心。这些催化剂正在选择性地构建在这些目标分子中发现的具有挑战性的结构。该单元的进一步转化导致沙棘溶素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，在吸引和留住教育管道中的少数族裔学生方面拥有独特的机会。JSU鼓励未被充分代表的少数族裔学生通过一个以研究为基础的教育项目从事STEM职业。该项目的成果与世界级的科学出版物、专业演讲和参加地区/国家会议有关，在这些会议上，学生们通过网络和全球化来扩展他们的职业培训和机会。在这项提议中，Hamme教授正在开发一条对映体选择性路线，以获得在沙参中发现的高度取代和不寻常的螺环-奥塞平核心。正在开发的路线包括由各种奎宁和手性尿素、硫脲和方酰胺有机催化剂催化的立体选择性的串联酮化/迈克尔加成反应序列。这些催化剂旨在活化酮，从而启动反应序列。这项工作正在解决一个合成挑战，这项研究的生物成分探索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学生正在接受培训，并面临着化学和生物相结合的挑战，扩大了他们在不同领域的接触，以及在学术界、政府实验室、制药行业和国防研究实验室的机会。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。

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.