New Cycloaddition and Annulation Strategies for Organic Synthesis

在这项由化学系化学合成计划支持的项目中，麻省理工学院化学系的Rick L.Danheiser教授将开发高效合成环状有机分子的新方法。这项研究计划的目标是开发新的策略，使碳环和杂环有机化合物的合成过程大大简化。周环反应作为这项研究的主要载体，主要致力于设计基于周环反应级联的收敛苯环策略。在拟议的研究中，将研究开发一种“串联策略”，在该策略中，基于乙烯基酮的苯环反应与各种杂环反应相结合，以提供有效的途径来获得包括吲哚和咔唑在内的高取代多环苯并稠合杂环体系。这一化学在抗氧化性生物碱安替他汀A1、抗真菌抗生素卡巴霉素A、海洋生物碱草丁C、氧化还原辅因子吡咯喹啉醌(PQQ)和电子有趣的五环杂环体系的合成中的应用将被研究。碳环和杂环体系被结合在许多生物重要化合物的结构中，开发高效的合成方法在提供更好的途径获得在医学、材料化学和许多其他领域具有重要应用的分子方面具有重要的价值。合成通常被描述为化学的“使能技术”。所开发的合成方法将为学术界和工业界的研究人员提供新的工具，用于合成在医药、农业、电子等领域具有应用价值的重要杂环化合物。该计划资助的研究生将接受培训，以发展他们作为合成化学家的技能，还将接受科学道德培训，并接受培训，以发展他们的口头和书面沟通技能。这些研究生还将担任麻省理工学院外展计划的协调员，该计划每年访问新英格兰地区约25所高中，提供关于化学和科学职业的演讲。每年大约有1200名高中生参加这些讲座，其中约35%的学生是代表不足的少数群体的成员。

In this project supported by the Chemical Synthesis Program of the Chemistry Division, Professor Rick L. Danheiser of the Department of Chemistry at the Massachusetts Institute of Technology will develop new methods for the efficient synthesis of cyclic organic molecules. The goal of this research program is the development of new strategies with the power to dramatically streamline the synthesis of carbocyclic and heterocyclic organic compounds. Pericyclic reactions serve as the primary vehicle to be exploited in this research, with most efforts focused on the design of convergent benzannulation strategies based on cascades of pericyclic reactions. In the proposed research, the development of a "tandem strategy" will be investigated in which a vinylketene based benzannulation reaction is employed in conjunction with various heterocyclization processes to provide efficient access to highly substituted polycyclic benzo-fused heterocyclic systems including indoles and carbazoles. The application of this chemistry to the synthesis of the antioxidant alkaloid antiostatin A1, the antifungal antibiotic carbazomycin A, the marine alkaloid herbindole C, the redox cofactor pyrroloquinoline quinone (PQQ), and an electronically interesting pentacyclic heteroaromatic system will be investigated.Carbocyclic and heterocyclic ring systems are incorporated in the structures of numerous biologically important compounds, and the development of highly efficient methods for their synthesis has great value in providing improved access to molecules with important applications in medicine, materials chemistry, and many other areas. Synthesis is often described as the "enabling technology" of chemistry. The synthetic methods developed in the proposed research will provide researchers in both academia and industry with new tools for the synthesis of important heterocyclic compounds with applications in medicine, agriculture, electronics, and other areas. The graduate students supported under this program will receive training to develop their skills as synthetic chemists, and will also receive training in scientific ethics and training to develop their oral and written communication skills. The graduate students will also serve as coordinators for the MIT Outreach Program which each year visits ca. 25 high schools in the New England region providing presentations on chemistry and careers in science. Approximately 1200 high school students attend these presentations each year, with ca. 35% of the students being members of underrepresented minority groups.