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

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.