New Reagents for Asymmetric Organic Synthesis from Engineered Cells

用于工程细胞不对称有机合成的新试剂

• 批准号: 0130315
• 负责人: Jon Stewart
• 金额: $ 39万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0130315&HistoricalAwards=false
• 关键词: New; Reagents; Asymmetric; Organic; Synthesis

The objectives of this work are two fold. Professor Stewart first proposes to use metabolically active but nongrowing E. coli cells to effect stereoselective organic functional group reduction reactions. E. coli cells will first be engineered to produce yeast reductases with desirable properties then quantities of the desired cells will be grown and used to effect syntheses of enantiomerically enriched, biologically relevant targets. The principal investigator will then investigate NADPH-dependent enzyme reactions again using nongrowing E. coli cells with the aim of developing whole cells capable of effecting either oxidation or reduction reactions depending on the amount of NAD/NADPH present. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Jon D. Stewart of the Department of Chemistry at the University of Florida. Dr. Stewart will work on the development of E. coli cells capable of catalyzing a number of chemical reactions. This group will explore stereoselective reduction reactions using enzymes contained in these whole cells. These reduction reactions produce molecules which are chiral (have two nonsuperimposable mirror images) and make only one of the two possible forms (a single enantiomer). Development of this family of reactions is one of the most important problems facing the pharmaceutical industry today. When developed, Dr. Stewart's work could be applied to the environmentally friendly syntheses of a number of biologically active molecules. Students trained during the course of this work will gain skills needed by the pharmaceutical industry which now produces a number of single enantiomer compounds.

这项工作的目标有两个。 Stewart教授首先提出使用代谢活跃但不生长的大肠杆菌细胞来实现立体选择性有机官能团还原反应。 大肠杆菌细胞将首先被工程化以产生具有所需特性的酵母还原酶，然后将生长大量所需细胞并用于实现对映体富集的、生物学相关靶标的合成。 然后，主要研究人员将使用非生长的大肠杆菌细胞再次研究 NADPH 依赖性酶反应，目的是开发能够根据 NAD/NADPH 存在量实现氧化或还原反应的完整细胞。有机和高分子化学项目通过该奖项支持佛罗里达大学化学系 Jon D. Stewart 博士的研究。 斯图尔特博士将致力于开发能够催化多种化学反应的大肠杆菌细胞。 该小组将利用这些全细胞中含有的酶探索立体选择性还原反应。 这些还原反应产生手性分子（具有两个不可重叠的镜像）并仅形成两种可能形式中的一种（单一对映体）。 这一系列反应的发展是当今制药工业面临的最重要的问题之一。 斯图尔特博士的研究成果开发完成后，可应用于多种生物活性分子的环保合成。 在这项工作过程中接受培训的学生将获得制药行业所需的技能，该行业现在生产许多单一对映体化合物。