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

RV Muralidhar, RR Chirumamilla, VN Ramachandran, R Marchant, Poonam Singh - Nee Nigam

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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. (C) 2002 Elsevier Science Ltd. All rights reserved.
LanguageEnglish
Pages1471-1475
JournalBIOORGANIC and; MEDICINAL CHEMISTRY
Volume10
Issue number5
Publication statusPublished - May 2002

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Proglumide
Candida
Esterification
Lipase
Cholecystokinin
Hexanols
Butanols
Hexanes
Organic solvents
Morphine
Mass spectrometry
Analgesics
Esters
Alcohols
Plasmas
Temperature
Peptides
Substrates
Enzymes
Pharmaceutical Preparations

Cite this

Muralidhar, RV ; Chirumamilla, RR ; Ramachandran, VN ; Marchant, R ; Singh - Nee Nigam, Poonam. / Resolution of (RS)-proglumide using lipase from Candida cylindraceae. In: BIOORGANIC and; MEDICINAL CHEMISTRY. 2002 ; Vol. 10, No. 5. pp. 1471-1475.
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abstract = "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. (C) 2002 Elsevier Science Ltd. All rights reserved.",
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Muralidhar, RV, Chirumamilla, RR, Ramachandran, VN, Marchant, R & Singh - Nee Nigam, P 2002, 'Resolution of (RS)-proglumide using lipase from Candida cylindraceae', BIOORGANIC and; MEDICINAL CHEMISTRY, vol. 10, no. 5, pp. 1471-1475.

Resolution of (RS)-proglumide using lipase from Candida cylindraceae. / Muralidhar, RV; Chirumamilla, RR; Ramachandran, VN; Marchant, R; Singh - Nee Nigam, Poonam.

In: BIOORGANIC and; MEDICINAL CHEMISTRY, Vol. 10, No. 5, 05.2002, p. 1471-1475.

Research output: Contribution to journalArticle

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AB - 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. (C) 2002 Elsevier Science Ltd. All rights reserved.

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