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.

在之前NSF的支持下，德克萨斯农工大学的Romo小组开发了实用的催化不对称路线，从酮酸底物中利用亲核剂催化的羟醛内酯化过程(NCAL)合成双环和三环β-内酯。在对NCAL过程日益了解的基础上，在化学部化学合成计划的支持下，正在寻求这些β-内酯的新转化和NCAL过程的新变体，包括动态动力学拆分。这些方法的实用性和实用性将在以完成海绵内酯和姜黄内酯/姜黄素内酯A为目标的天然产物全合成的背景下得到证明。此外，将制备基于这些生物活性天然产物的特定细胞探针，作为合作研究中的基本蛋白质组学工具。烯醇酸铵的机理研究旨在开发涉及这些多功能中间体的新反应流形，正在与迪恩·坦蒂洛教授(加州大学戴维斯分校)合作进行。有机合成的做法继续有助于推动在人类和动物健康等领域取得重大进展。拟议的β-内酯方法的成功开发将影响与制药和农业相关的有机合成领域，因为正在开发的方法是强大的和“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了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。ROMO集团发起了一系列外联活动，包括在年度化学开放日期间建立天然产品发现实验室，通过将新实验引入化学专业实验室来结合NSF资助的研究和教学，以及开发多媒体演示文稿来展示有机合成的社会相关性。