Novel Asymmetric Routes to 2-Oxetanones and their Application

2-氧杂环丁酮的新型不对称合成路线及其应用

• 批准号: 1112397
• 负责人: Daniel Romo
• 金额: $ 42.5万
• 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: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1112397&HistoricalAwards=false
• 关键词: Novel; Asymmetric; Routes; Oxetanones; their

Under prior NSF support, the Romo Group at Texas A&M University developed practical, catalytic asymmetric routes to both bicyclic and tricyclic beta-lactones from ketoacid substrates employing a nucleophile-catalyzed aldol lactonization process (NCAL). Building on a growing understanding of the NCAL process, novel transformations of these beta-lactones and new variants of the NCAL process including dynamic kinetic resolution are being pursued with the support from the Chemical Synthesis Program of the Division of Chemistry. The utility and practicality of these methods will be demonstrated in the context of natural product total synthesis targeting the completion of spongiolactone and curcumalactone/curcumanolide A. In addition, specific cellular probes based on these bioactive natural products will be prepared to serve as basic proteomics tools in collaborative studies. Mechanistic studies of ammonium enolates directed toward development of new reaction manifolds involving these versatile intermediates are being pursued in collaboration with Prof. Dean Tantillo (UC Davis). The practice of organic synthesis continues to be instrumental in propelling significant advances in the areas of human and animal health among other fields. Successful development of the proposed methods for beta-lactones will impact the field of organic synthesis pertinent to the pharmaceutical and agricultural industries as the methods being developed are robust and "user friendly". In addition, synthesis of the targeted biologically active natural products by synthetic methods being developed will have broader impacts in enabling the further understanding of fundamental cellular processes and enabling collaborations with computational chemists and biochemists/cell biologists. The Romo Group has initiated a number of outreach initiatives including a Natural Products Discovery Lab during the Annual Chemistry Open House, combining NSF-funded research and teaching by importing new experiments into the chemistry major's laboratory, and developing multimedia presentations to demonstrate the societal relevance of organic synthesis.

在先前的NSF支持下，得克萨斯州A＆M大学的ROMO组从酮酸基质底物中开发了实用的，催化的不对称途径，从而从酮酸底物中使用了使用核磷脂催化的藻类醛醛醛酸酯乳酸盐化过程（Ncal）的酮酸基质。 在对NCAL过程的越来越多的理解之下，这些β-内酯的新型转换和NCAL过程的新变体（包括动态动力学分辨率）的新变化得到了化学化学综合计划的支持。 这些方法的实用性和实用性将在天然产物全合成的背景下进行证明，这是针对海绵乳突和姜黄酮/姜黄素A的完成的。此外，基于这些生物活性天然产物的特定细胞探针还可以作为协作研究中的基本蛋白质组学工具做好准备。针对开发涉及这些多功能中间体的新反应歧管的铵烯醇的机理研究正在与Dean Tantillo教授（UC Davis）合作进行。有机综合的实践继续在推动其他领域的人类和动物健康领域的重大进步中发挥作用。 随着开发的方法的强大和“用户友好”，成功地开发了β-内酯的方法将影响与制药和农业产业有关的有机合成领域。此外，通过开发合成方法对有针对性的生物活性天然产物的合成将对能够进一步了解基本细胞过程产生更广泛的影响，并与计算化学家和生物化学家/细胞生物学家合作。 罗莫集团（Romo Group）在年度化学开放日期间发起了许多外展计划，包括天然产品发现实验室，通过将新实验进口到化学专业的实验室，并开发多媒体演讲以证明有机合成的社会相关性，从而结合了NSF资助的研究和教学。