Exploring N-Alkynylazole Cyclizations in Synthesis

有了这个奖项，NSF化学部的化学合成计划正在支持德克萨斯州立大学的Sean Kerwin教授的研究。 Kerwin博士与本科生、研究生和博士后一起工作，以简化制备复杂化合物的过程。 具有含氮环系的化合物在自然界中非常常见，并且通常具有有趣的生物活性。 在这项研究中，这些化合物的具体例子是有针对性的合成，所制备的化合物将可用于解决重要的生物学问题。 用于这些合成的科学方法集中于利用较简单的起始材料来制备结构复杂的、具有生物活性的天然产物。 开展的教育活动通过在采用实验室自动化的跨学科团队中进行培训，为学生在STEM领域的职业生涯做好准备。3D打印材料的设计和制作是3D打印材料的重要组成部分，它将为学生和公众展示化学的历史、结构和医学影响。复杂的杂环天然产物和相关生物有趣化合物的高效合成对制药、农用化学品、材料和其他领域具有广泛的潜在影响。 杂环化合物的逆合成分析揭示了简化的断开导致N-炔基唑中间体，其中乙炔基团键合到五元杂芳环的氮原子上。 Kerwin教授正在开发环化反应，以使这些简化的断开以及其他方法获得必要的N-炔基唑。在合成喷司他丁、morodin和石松素天然产物的类似物中，正在采用多种环化策略，包括高炔丙基系统的5-内切环化、N-炔基唑的吲哚化和1，x-二炔基唑的热重排。除了提供获得目标化合物作为生物研究工具之外，这项工作的更广泛影响来自其对不同合成目标的广泛潜在适用性。 其他更广泛的影响包括通过研究培训经验招募代表性不足的学生从事科学，技术，工程和数学（STEM）职业。 这些培训经验包括实验室自动化系统的使用，以及针对学生和公众开展的以自然产品对社会的影响为重点的外联活动。该奖项反映了NSF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。

With this Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Sean Kerwin of Texas State University. Dr. Kerwin works with undergraduate and graduate students and postdocs to streamline the process of preparing complex chemical compounds. Compounds with nitrogen-containing ring systems are very common in nature and often possess interesting biological activity. In this research, specific examples of these compounds are targeted for synthesis, and the prepared compounds will be made available to address important biological questions. The scientific approach employed for these syntheses focuses on the utilization of simpler starting materials to prepare structurally complex, biologically active natural products. The educational activities undertaken prepare students for careers in STEM through training in an interdisciplinary team employing laboratory automation. Outreach activities include the design and preparation of 3D printed materials to highlight the historical, structural, and medicinal impacts of chemistry for students and the broader public.The efficient synthesis of complex heterocyclic natural products and related biologically-interesting compounds has broad potential impact on pharmaceuticals, agrochemicals, materials, and other areas. Retrosynthetic analyses of heterocyclic compounds reveal simplifying disconnections leading to N-alkynylazole intermediates, in which an acetylene group is bonded to the nitrogen atom of a five-membered heteroaromatic ring. Professor Kerwin is developing cyclization reactions to enable these simplifying disconnections as well as other methods to access the requisite N-alkynylazoles. Multiple cyclization strategies are being pursued in the synthesis of analogs of pentostatin, morodin, and lycoposerrine natural products, including 5-endo-dig cyclization of homopropargylic systems, indolization of N-alknynylazoles, and thermal rearrangements of 1,x-dialkynylazoles. In addition to providing access to the targeted compounds as tools for biological research, the broader impact of this work derives from its wide potential applicability to diverse synthetic targets. Other broader impacts include the recruitment of underrepresented students to science, technology, engineering and mathematics (STEM) careers through research training experiences. These training experiences include the use of laboratory automation systems and the implementation of outreach activities for students and the public focused on the impact of natural products on society.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.