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.

这项工作有两个目标。 斯图尔特教授首先提出使用代谢活跃但不生长的E。coli细胞中进行立体选择性有机官能团还原反应。 E.首先将大肠杆菌细胞工程化以产生具有所需性质的酵母还原酶，然后将大量的所需细胞生长并用于实现对映体富集的生物学相关靶的合成。 然后，主要研究者将使用非生长的E.大肠杆菌细胞，目的是开发能够根据存在的NAD/NADPH的量进行氧化或还原反应的全细胞。有了这个奖项，有机和高分子化学计划是支持博士的研究。佛罗里达大学化学系的斯图尔特说。 斯图尔特博士将致力于E.能够催化许多化学反应的大肠杆菌细胞。 这个小组将探索立体选择性还原反应，使用酶包含在这些整个细胞。 这些还原反应产生的分子是手性的（有两个不可重叠的镜像），并且只产生两种可能形式之一（单一对映异构体）。 这类反应的发展是当今制药工业面临的最重要的问题之一。 Stewart博士的研究成果一经开发，就可以应用于许多生物活性分子的环境友好合成。 在这项工作的过程中培训的学生将获得制药行业所需的技能，现在生产一些单一的对映体化合物。