PRODUCTION OF OPTICALLY PURE 2 ARYLPROPIONIC ACIDS

光学纯 2 芳基丙酸的生产

• 批准号: 2656486
• 负责人: STEVEN D DIETZ
• 金额: $ 10万
• 依托单位: TDA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2656486
• 关键词: catalyst; chemical synthesis; drug design /synthesis /production; method development; nonsteroidal antiinflammatory agent; propionates; protonation; racemization; stereochemistry; stereoisomer

Drugs based on 2-arylpropionic acids have become increasingly important for use as analgesics and anti-inflammatory agents. Examples are naproxen, ibuprofen and ketoprofen; sales of prescription and nonprescription drugs of this type represent a $5 billion market. Although 2-arylpropionic anti-inflammatory drugs are sold as racemic mixtures, extensive pharmacological studies have shown that one enantiomer of these compounds is generally more effective than the other. For example, S-naproxen is about 28 times more effective its R-isomer. Unfortunately, typical production methods for 2-arylpropionic acids yield racemic mixtures and require expensive and time-consuming optical resolutions to obtain optically pure products. A more desirable way to prepare 2-arylpropionic acids would be to enantioselectively hydrogenate the carbon-carbon double bond (C=C) groups of 2-arylpropionic acid precursors. This direct synthesis route could lower costs because only the desired product would be formed, avoiding the expense of a chiral separation. Unfortunately, the current catalysts cannot be easily separated from the reaction mixture. The objective of the proposal is to develop a new catalytic process that allows easy catalyst removal and reuse to show that a variety of 2-arylpropionic acids can be economically produced by asymmetric hydrogenation. PROPOSED COMMERCIAL APPLICATIONS: This research will lead to the development of a general method for the production of optically pure 2-arylpropionic acids by the enantioselective hydrogenation of compounds with C=C bonds. This will allow the economical production of valuable 2-arylpropionic acids for use as analgesics and anti-inflammatory agents.

基于2-芳丙酸的药物已经变得越来越重要 用作镇痛药和抗炎药。例如 萘普生，布洛芬和酮芬；处方销售和 这种类型的非处方药代表了50亿美元的市场。 虽然2-芳基发酵抗炎药以消极的形式出售 混合物，广泛的药理学研究表明 这些化合物的对映异构体通常比其他化合物更有效。 例如，S-Naproxen的R-Isomer效率约为28倍。 不幸的是，2-芳基丙酸的典型生产方法产生 极端混合物，需要昂贵且耗时的光学 获得光学纯产品的决议。 制备2-芳基丙酸的一种更理想的方法是 对映选择性氢化碳碳双键（C = C）组 2-芳基丙酸的前体。这种直接的合成路线可以 较低的成本是因为只会形成所需的产品，避免 手性分离的费用。不幸的是，当前的催化剂 不能轻易地与反应混合物分离。目的 该建议是开发一个新的催化过程，可以轻松 催化剂去除并重复使用以表明各种2-芳族植物 酸可以通过不对称的氢化在经济上产生。 拟议的商业应用： 这项研究将导致开发一种通用方法 生产光学纯的2-芳基丙酸 具有C = C键的化合物的对映选择性氢化。这会 允许经济生产有价值的2-芳基丙酸供使用 作为镇痛药和抗炎药。

项目成果

Rescue of cerebellar granule cells from death in weaver NR1 double mutants.

拯救编织者 NR1 双突变体中的小脑颗粒细胞免于死亡。

• DOI: 10.1523/jneurosci.19-18-07991.1999
• 发表时间: 1999
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Jensen,P;Surmeier,DJ;Goldowitz,D
• 通讯作者: Goldowitz,D