有机化学 ›› 2020, Vol. 40 ›› Issue (1): 215-220.DOI: 10.6023/cjoc201908008 上一篇    下一篇

研究简报

糖苷酶底物6-氯-4-甲基伞形酮-α-L-艾杜糖醛酸苷的合成

田加蒙, 宁倩倩, 丁海新, 柏江, 肖强   

  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
  • 收稿日期:2019-08-05 修回日期:2019-09-04 出版日期:2020-01-25 发布日期:2019-09-25
  • 通讯作者: 丁海新, 肖强 E-mail:dinghaixin_2010@163.com;xiaoqiang@tsinghua.org.cn
  • 基金资助:
    国家自然科学基金(Nos.21462019,21676131)、江西省科技厅重点(No.20143ACB20012)和江西科技师范大学博士启动基金(No.2018BSQD022)资助项目.

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

Tian Jiameng, Ning Qianqian, Ding Haixin, Bai Jiang, Xiao Qiang   

  1. Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science & Technology Normal University, Nanchang 330013
  • Received:2019-08-05 Revised:2019-09-04 Online:2020-01-25 Published:2019-09-25
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Nos. 21676131, 21462019), the Bureau of Science & Technology of Jiangxi Province (No. 20143ACB20012) and the Doctor Startup Fund of Jiangxi Science & Technology Normal University (No. 2018BSQD022).

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.

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

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-idopyra-nosiduronic 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.

Key words: α-L-iduronidase, fluorogenic enzyme substrate, Mitsunobu reaction, glycosylation, radical reaction