PRODUCTION OF OPTICALLY PURE 2 ARYLPROPIONIC ACIDS

光学纯 2 芳基丙酸的生产

基本信息

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
项目类别：
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

项目摘要

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-芳基丙酸的药物变得越来越重要用作镇痛剂和抗炎剂。例子是萘普生、布洛芬和酮洛芬；处方药销售和此类非处方药代表着 50 亿美元的市场。尽管 2-芳基丙酸抗炎药以外消旋形式出售混合物，广泛的药理学研究表明，一种这些化合物的对映体通常比其他化合物更有效。例如，S-萘普生的功效比其 R 异构体高出约 28 倍。不幸的是，2-芳基丙酸的典型生产方法会产生外消旋混合物，需要昂贵且耗时的光学决议获得光学纯的产品。制备 2-芳基丙酸的更理想的方法是对映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降低成本，因为只形成所需的产品，避免手性分离的费用。不幸的是，目前的催化剂不能轻易地从反应混合物中分离出来。的目标该提案是开发一种新的催化工艺，可以轻松实现催化剂的去除和再利用表明多种2-芳基丙酸酸可以通过不对称氢化经济地生产。拟议的商业应用：这项研究将导致开发一种通用方法光学纯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。这将可以经济地生产有价值的 2-芳基丙酸以供使用作为镇痛剂和抗炎剂。