Synthesis of 1-β-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

被引:31
作者
Baba, Akiko [1 ]
Yoshioka, Tadao [1 ]
机构
[1] Hokkaido Pharmaceut Univ Sch Pharm, Dept Pharm, Otaru, Hokkaido 0470264, Japan
关键词
D O I
10.1039/b608755h
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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).
引用
收藏
页码:3303 / 3310
页数:8
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