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.
Muralidhar
R V
RV
School of Biomedical Sciences, University of Ulster at Coleraine, N. Ireland BT52 1SA, UK.
Chirumamilla
R R
RR
Ramachandran
V N
VN
Marchant
R
R
Nigam
P
P
D000700:Analgesics / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D002175:Candida / Q000201:enzymology; D004951:Esterification; D008049:Lipase / Q000378:metabolism*; D013058:Mass Spectrometry; D011377:Proglumide / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D012997:Solvents / Q000494:pharmacology; D013237:Stereoisomerism
D000700:Analgesics; D000897:Anti-Ulcer Agents; D012997:Solvents; D008049:Lipase; D011377:Proglumide