Resolution of (RS)-proglumide using lipase from Candida cylindraceae.

Proglumide is used in the treatment of neuropathic pain. It acts by inhibiting peptide cholecystokinin (CCK). Neural injury produces an elevation in plasma CCK. Proglumide has been also shown to augment the analgesic effect of sustained release morphine in neuropathic pain. Currently proglumide is administered as a racemic mixture. In the present study, an attempt is made to separate the racemic mixture of the drug using lipase obtained from Candida cylindracea by stereoselective esterification. Enzymatic stereoselective esterification was carried out in organic solvents. The resolution was studied using a chromatographic column with a chiral support and mass spectrometry. The reaction conditions for stereoselective esterification including amount of substrate, amount of enzyme, alcohol, solvent and temperature were optimised during the present investigation. Butanol and hexanol were found to be suitable for formation of S and R esters, respectively. Hexane was the best solvent for esterification and the optimum temperature was found to be 30 degreesC.

Racemic resolution of RS-baclofen using lipase from Candida cylindracea.

Baclofen is chemically (RS)-beta-(aminomethyl)-4-chlorobenzene propanoic acid. It is used in therapy of pain and as a muscle relaxant. Baclofen produces analgesia by increasing the concentration of gamma amino butyric acid (GABA), the major rapid inhibitory transmitter. Both the isomers of baclofen have different therapeutic activity with respect to their interaction to the receptors at the site of action. Lipase from Candida cylindracea has been used as a catalyst for resolving racemic mixtures of numerous drug molecules. The present investigation deals with the racemic resolution of RS-baclofen using lipase from Candida cylindracea and a study of the factors affecting resolution.