Novel Asymmetric Routes to 2-Oxetanones and their Application

在先前的NSF支持下，德克萨斯A M大学的Romo小组开发了实用的催化不对称路线，采用亲核催化的羟醛内酯化过程（NCAL）从酮酸底物制备双环和三环β-内酯。 基于对NCAL过程的不断了解，这些β-内酯的新转化和NCAL过程的新变体（包括动态动力学拆分）正在化学部化学合成计划的支持下进行。 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，以海绵内酯和姜黄内酯/姜黄素A的完成为目标来证明。 此外，基于这些生物活性天然产物的特异性细胞探针将被制备，作为合作研究中的基本蛋白质组学工具。与Dean Tantillo教授（加州大学戴维斯分校）合作，正在进行烯醇化铵的机理研究，旨在开发涉及这些多功能中间体的新反应歧管。有机合成的实践继续推动人类和动物健康等领域的重大进展。 所提出的用于β-内酯的方法的成功开发将影响与制药和农业工业相关的有机合成领域，因为所开发的方法是稳健的和“用户友好的”。此外，通过正在开发的合成方法合成目标生物活性天然产物将在进一步理解基本细胞过程以及与计算化学家和生物化学家/细胞生物学家合作方面产生更广泛的影响。 罗莫集团已经启动了一些推广活动，包括在年度化学开放日期间的天然产品发现实验室，通过将新实验导入化学专业的实验室，将NSF资助的研究和教学结合起来，并开发多媒体演示文稿，以展示有机合成的社会意义。

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.