Synthesis of 1-beta-O-acyl glucuronides of diclofenac, mefenamic acid and (S)-naproxen by the chemo-selective enzymatic removal of protecting groups from the corresponding methyl acetyl derivatives.
Using a straightforward chemo-enzymatic procedure, 1-beta-O-acyl glucuronides of three non-steroidal anti-inflammatory drugs, diclofenac (DF) 5, mefenamic acid (MF) 6 and (S)-naproxen (NP) 7, were prepared. Caesium salts of these carboxylic acid drugs reacted with commercially available methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-alpha-D-glucopyranuronate 4 to give exclusively the corresponding 1-beta-O-acyl glucuronides 8-10 in moderate yields. The protecting acetyl (for -OH group) and methyl ester (for -CO2H group) groups of each sugar moiety were easily removed to provide the corresponding free 1-beta-O-acyl glucuronides 1-3 in high yields. Deprotection was achieved through effective enzyme-catalysed chemo-selective hydrolyses of the acetyl groups using lipase AS Amano (LAS), and of the methyl ester group using esterase from porcine liver (PLE).
Baba
Akiko
A
Department of Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, Otaru, 047-0264, Hokkaido, Japan.
Yoshioka
Tadao
T
D000215:Acylation; D002236:Carbohydrate Conformation; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac; D020719:Glucuronides / Q000138:chemical synthesis* / Q000737:chemistry; D006868:Hydrolysis; D007700:Kinetics; D008528:Mefenamic Acid; D008745:Methylation; D008958:Models, Molecular; D009288:Naproxen
D020719:Glucuronides; D004008:Diclofenac; D008528:Mefenamic Acid; D009288:Naproxen