ASYMMETRIC SYNTHESIS OF 13C LABELED AMINO ACIDS

13C标记氨基酸的不对称合成

• 批准号: 2546021
• 负责人: DIEM D LE
• 金额: $ 37.17万
• 依托单位: LE RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2546021
• 关键词: aminoacid; carbon; chemical synthesis; gas chromatography; method development; nuclear magnetic resonance spectroscopy; radiotracer

New preparative methods that provide a reliable source for stable-isotope labeled amino acids suitable for NMR study of membrane proteins are needed for further advances in this field. Phase I demonstrated the synthetic steps leading to optically pure, 13C-labeled leucine, tyrosine and threonine as proposed. The synthesis involved modifications of existing methods to obtain >99% diastereomeric excess and eliminate the need for further chromatographic purification. Subsequent hydrolytic steps were effected without detectable racemization. The chiral auxiliaries were satisfactorily recovered. The results suggest the selected approach as a viable commercial production method. Phase II aims to continue developing the preparative methods for all 21 major proteinogenic amino acids each 13C-labeled at every other position. Synthesis of the requisite labeled side chains will be facilitated by the availability of some new labeled precursors recently developed in our lab. In addition, a new simple extractive technique for separating and recovering the expensive chiral auxiliary. which should lower the production costs considerably. will be pursued. The amino acids will have a 99% enantiomeric excess minimum and 99% 13C-enrichment at all intended positions. PROPOSED COMMERCIAL APPLICATION: In addition to NMR, the labeled amino acids are also useful for metabolic study and as internal standards for GC-MS quantitative analysis. Other potential spin-offs are promising. The commercial potentials appear quite considerable.

为稳定同位素提供可靠来源的新制备方法 适合于膜蛋白核磁共振研究的标记氨基酸有 这是在这一领域取得进一步进展所需要的。第一阶段演示了 合成步骤导致光学纯度，13C标记的亮氨酸，酪氨酸 以及提议的苏氨酸。该合成涉及到对 现有方法可获得99%的非对映异构体过剩并消除 需要进一步的层析纯化。后续水解物 在没有检测到外消旋的情况下进行了步骤。手性 助剂的回收情况令人满意。结果表明， 选定的方法作为一种可行的商业生产方法。第二阶段目标 继续开发所有21个主要项目的准备方法 蛋白原氨基酸，每个13C标记在每一个其他位置。 必要的标记侧链的合成将通过 我们最近开发的一些新标记前体的可用性 实验室。此外，一种新的简单的萃取技术分离和 回收昂贵的手性助剂。这应该会降低 生产成本相当高。将会被追查。氨基酸将会有 99%的对映体过量最低限度和99%的13C-富集度 各就各位。 拟议的商业应用：除了核磁共振，标记的氨基 酸对新陈代谢研究也很有用，并可作为 GC-MS定量分析。其他潜在的衍生产品前景看好。这个 商业潜力似乎相当可观。