糖苷酶底物6-氯-4-甲基伞形酮-α-L-艾杜糖醛酸苷的合成  

Synthesis of Enzyme Substrate 6-Chloro-4-methylumbelliferyl-α-L-idopyranosiduronic Acid

作　　者：田加蒙 宁倩倩 丁海新[1] 柏江[1] 肖强[1] Tian Jiameng;Ning Qianqian;Ding Haixin;Bai Jiang;Xiao Qiang(Jiangxi Key Laboratory of Organic Chemistry,Jiangxi Science&Technology Normal University,Nanchang 330013)

机构地区：[1]江西科技师范大学有机功能分子研究所江西省有机功能分子重点实验室,南昌330013

出　　处：《有机化学》2020年第1期215-220,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.21462019,21676131);江西省科技厅重点(No.20143ACB20012);江西科技师范大学博士启动基金(No.2018BSQD022)资助项目。

摘　　要：为了开发用于粘多糖贮积症I型疾病检测的α-L-艾杜糖醛酸荧光酶底物,以廉价易得的葡醛酸内酯为起始原料合成1,2,3,4-四-O-乙酰基-β-D-葡萄糖醛酸甲酯,经过自由基溴代及自由基还原合成1,2,3,4-四-O-乙酰基-α-L-艾杜糖糖醛酸甲酯,以Mitsunobu反应为关键步骤合成糖苷键,最后脱除保护基团得到6-氯-4-甲基伞形酮-α-L-艾杜糖醛酸苷.用单晶衍射确证了关键中间体的结构,初步的酶学测试证明该底物可用于α-L-艾杜糖醛酸酶活性的快速检测.In order to develop fluorogenic enzyme substrate for quick diaganosis of mucopolysaccharidosis type I,6-chloro-4-methylumbelliferyl-α-L-idopyranosiduronic acid was synthesized from commercially available D-glucurono-6,3-lactone. Firstly, 1,2,3,4-tetra-O-acetyl-β-D-glucoronate methyl ester was brominated and subsequently reduced with radical reaction to give 1,2,3,4-tetra-O-acetyl-L-idopyranuronate methyl ester. Then 6-chloro-4-methylumbelliferyl-α-L-idopyranosiduronic acid was synthesized using Mitsunobu reaction as the key step. The related structures of key intermediates were confirmed with X-ray crystallography. The preliminary biological test proved that the synthesized enzyme substrate could be used for quick detection of α-L-iduronidase.

关 键 词：α-L-艾杜糖醛酸酶 荧光酶底物 MITSUNOBU反应 糖苷化 自由基反应 

分 类 号：R914[医药卫生—药物化学]