Production of Optically Pure 2 Arylpropionic Acids

Period of Performance: 08/01/1998 - 04/30/1999

Unknown

Phase 1 SBIR

Recipient Firm

TDA Research, Inc.
12345 W. 52nd Ave. Array
Wheat Ridge, CO 80033
Principal Investigator

Abstract

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.