PRODUCTION OF OPTICALLY PURE 2 ARYLPROPIONIC ACIDS

基于2-芳基丙酸的药物变得越来越重要 用作镇痛剂和消炎药。以下是例子 萘普生、布洛芬、酮洛芬；处方和 这类非处方药代表着50亿美元的市场。 尽管2-芳基丙酸消炎药作为外消旋出售 混合物，广泛的药理研究表明一种 这些化合物的对映体通常比另一种更有效。 例如，S-萘普生的效果大约是其R-异构体的28倍。 不幸的是，2-芳基丙酸的典型生产方法 外消旋混合物，需要昂贵和耗时的光学 获得光学纯产品的决心。 制备2-芳基丙酸的更可取的方法是 对映体选择性氢化碳-碳双键(C=C)基团 2-芳基丙酸前体。这种直接合成路线可以 更低的成本，因为只会形成所需的产品，避免了 手性分离的费用。不幸的是，目前的催化剂 不易从反应混合物中分离出来。的目标是 该提议是开发一种新的催化过程，使 催化剂的去除和重复使用表明各种2-芳基丙酸 通过不对称氢化可以经济地生产酸。 建议的商业应用： 这项研究将导致开发一种通用的方法 光学纯2-芳基丙酸的生产 具有C=C键的化合物的对映选择性氢化。这将是 允许经济地生产有价值的2-芳基丙酸供使用 作为镇痛剂和消炎药。

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.