Exploring N-Alkynylazole Cyclizations in Synthesis

探索合成中的 N-炔唑环化

• 批准号: 1955432
• 负责人: Sean Kerwin
• 金额: $ 49万
• 依托单位: Texas State University - San Marcos
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955432&HistoricalAwards=false
• 关键词: Exploring; Alkynylazole; Cyclizations; Synthesis

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.

美国国家科学基金会化学部的化学合成项目用这个奖项来支持德克萨斯州立大学肖恩·克尔温教授的研究。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。含氮环系统的化合物在自然界中非常常见，往往具有有趣的生物活性。在本研究中，这些化合物的具体例子将被用于合成，所制备的化合物将可用于解决重要的生物学问题。这些合成所采用的科学方法侧重于利用更简单的起始材料来制备结构复杂、具有生物活性的天然产物。所开展的教育活动通过在跨学科团队中使用实验室自动化的培训，为学生在STEM领域的职业生涯做好准备。外展活动包括设计和制备3D打印材料，以突出化学对学生和广大公众的历史、结构和医学影响。复杂杂环天然产物及相关的生物活性化合物的高效合成在医药、农用化学品、材料等领域具有广泛的潜在影响。杂环化合物的反合成分析揭示了简化分离导致n -炔基唑中间体，其中乙炔基团与五元杂芳环的氮原子结合。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所需的n -炔基唑。多种环化策略被用于合成戊他汀、莫洛丁和番茄丝氨酸天然产物的类似物，包括同丙炔基体系的5-内环化、n -炔基唑的吲哚化和1，x-二炔基唑的热重排。除了为生物学研究提供获得目标化合物的工具外，这项工作的更广泛影响还来自于它对各种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。这些培训经验包括使用实验室自动化系统，以及为学生和公众开展外联活动，重点关注天然产品对社会的影响。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。

项目成果

Spirocyclic Products via Carbene Intermediates from Thermolysis of 1,2-Dialkynylpyrrole and 1,2-Diethynylimidazole

1,2-二炔基吡咯和 1,2-二乙炔咪唑热解生成卡宾中间体的螺环产物

• DOI: 10.1055/s-0041-1737937
• 发表时间: 2022
• 期刊: Synlett
• 影响因子: 2
• 作者: Jewett, Ashley L.;Bondoc, Joshua A.;Gilbreath, Bradford L.;Reinus, Brandon J.;Kerwin, Sean M.
• 通讯作者: Kerwin, Sean M.