Resolution of 4-amino-cyclopentanecarboxylic acid methyl esters using hydrolytic enzymes.
A number of esterases (EC 3.1.1.1) and lipases (EC 3.1.1.3) of microbial and mammalian origin were screened for the ability to resolve racemic 4-amino-cyclopentanecarboxylic acid methyl ester derivatives as potential intermediates in the production of carbocyclic nucleosides. Surprisingly, functionalization of the remote amino group had a profound effect on both the rate and enantioselectivity of hydrolysis of the methyl ester. 4-(Benzoylamino)-2-cyclopentenecarboxylic acid, methyl ester (V) with pig liver esterase gave the highest enantioselectivity. The residual ester, which was of the correct absolute stereochemistry [(+) 1S, 4R] for carbocyclic nucleoside synthesis, could be obtained in high optical purity. Optimization of pH, solvent type, and concentration improved the enantioselectivity of the process by a further twofold.
Department of Natural Products Discovery, Glaxo Group Research Ltd, Greenford, Middlesex, England.
M
M
Mahmoudian
B S
BS
Baines
M J
MJ
Dawson
G C
GC
Lawrence
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000302:isolation & purification*; D002175:Candida / Q000201:enzymology; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000302:isolation & purification*; D004950:Esterases / Q000378:metabolism*; D007202:Indicators and Reagents; D008049:Lipase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D011549:Pseudomonas / Q000201:enzymology; D012233:Rhizopus / Q000201:enzymology; D012997:Solvents; D013237:Stereoisomerism; D013379:Substrate Specificity; D013552:Swine
D000935:Antifungal Agents; D003517:Cyclopentanes; D007202:Indicators and Reagents; D012997:Solvents; D004950:Esterases; D008049:Lipase