Novel Asymmetric Routes to 2-Oxetanones and Their Application

2-氧杂环丁酮的新型不对称路线及其应用

• 批准号: 0809747
• 负责人: Daniel Romo
• 金额: $ 40.5万
• 依托单位: Texas A&M Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0809747&HistoricalAwards=false
• 关键词: Novel; Asymmetric; Routes; Oxetanones; Their

This project will continue work on the development of concise methods for the asymmetric synthesis of novel beta-lactones (2-oxetanones) via organocatalysis. In particular, further development of Lewis base-promoted, aldol-lactonizations (net cycloadditions) that construct a C-C bond and a C-O bond simultaneously will be pursued to access these versatile strained heterocycles. In addition to studies of novel Lewis-base promoters, mechanistic studies will be undertaken to gain further insights into the overall reaction pathway including a potential acyl substitution proceeding via an SN2 pathway. In addition, novel transformation of these heterocycles including ring expansions by way of dyotropic rearrangements of bicyclic and tricyclic beta-lactones will be explored further. Hypothesis driven studies of novel reaction pathways involving ammonium enolates and including extended and interrupted Morita-Baylis-Hillman processes will be pursued. The utility of the methods and processes developed will be highlighted by applications to the total synthesis of spongiolactone and curcumalactone. With respect to educational objectives, the translation of laboratory research into the teaching laboratory will continue along with further development of multimedia approaches for conveying the societal relevance of organic synthesis.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Daniel Romo of the Department of Chemistry at Texas A&M University. Professor Romo's research efforts revolve around the development of catalytic, asymmetric methods for the synthesis of beta-lactones and their application in synthesis including natural product total synthesis. The results of this research will contribute significantly to further use and application of these underutilized heterocycles, which possess a diverse array of reactivity modes making them highly versatile intermediates for organic synthesis. Successful development of the proposed methods will have an impact on organic synthesis in the pharmaceutical and agricultural industries as the methods being developed are robust and "user friendly." In addition, synthesis of the targeted natural products will have broader impacts in enabling the further understanding of fundamental cellular processes.

本项目将继续致力于开发通过有机催化不对称合成新型β -内酯（2-氧乙酮）的简明方法。特别是，进一步发展路易斯碱促进的醛酮内酯化（净环加成），同时构建一个C-C键和一个C-O键，以获得这些多功能应变杂环。除了对新型lewis碱启动子的研究外，还将进行机理研究，以进一步了解整个反应途径，包括通过SN2途径进行酰基取代的潜在过程。此外，这些杂环的新转化，包括通过双环和三环-内酯的各向异性重排进行环扩张，将进一步探索。假设驱动的研究涉及烯醇化铵的新反应途径，包括延长和中断的森田-贝利斯-希尔曼过程。所开发的方法和工艺的效用将通过在海绵内酯和姜黄内酯的全合成中的应用而得到强调。就教育目标而言，将实验室研究转化为教学实验室将继续与多媒体方法的进一步发展一起，以传达有机合成的社会相关性。通过这个奖项，有机和大分子化学项目支持了德克萨斯农工大学化学系丹尼尔·罗莫教授的研究。Romo教授的研究工作围绕着催化、不对称合成-内酯方法的发展及其在合成中的应用，包括天然产物的全合成。这些未充分利用的杂环化合物具有多种反应模式，是有机合成中用途广泛的中间体，本研究结果将为进一步利用和应用这些杂环化合物做出重要贡献。所提出的方法的成功开发将对制药和农业行业的有机合成产生影响，因为正在开发的方法是稳健和“用户友好”的。此外，目标天然产物的合成将对进一步了解基本细胞过程产生更广泛的影响。