新型含亚氨基糖的UDP-Galf模拟物的非对映选择性合成：UDP-Gal变位酶和UDP-Galf转移酶的潜在抑制剂

Diastereoselective synthesis of novel iminosugar-containing UDP-Galf mimics: potential inhibitors of UDP-Gal mutase and UDP-Galf transferases.

作者信息

Liautard Virginie, Christina Alphert E, Desvergnes Valérie, Martin Olivier R

机构信息

Institut de Chimie Organique et Analytique, CNRS and Université d'Orléans, BP 6759, 45067 Orléans, France.

出版信息

J Org Chem. 2006 Sep 15;71(19):7337-45. doi: 10.1021/jo061130e.

DOI:10.1021/jo061130e

PMID:16958528

Abstract

Tetra-O-benzyl-D-glucofuranose was converted into uridine diphosphono-beta-Galf mimics based on an iminosugar skeleton linked to UMP by a 2-hydroxypropyl tether. The synthesis is based on the highly regio- and stereoselective cycloaddition of an original uridin-5'-yl allylphosphonate with a 1,4-dideoxy-1,4-iminogalactitol-derived cyclic nitrone, followed by the reductive elaboration of the cycloaddition product. The resulting iminogalactose-UMP conjugates are novel sugar nucleotide mimics which could be useful as inhibitors of UDP-Gal mutase and UDP-Galf transferases.

摘要

四 - O - 苄基 - D - 呋喃葡萄糖通过2 - 羟丙基连接基转化为基于与尿苷 - 5'- 单磷酸（UMP）相连的亚氨基糖骨架的尿苷二磷酸 - β - Galf模拟物。该合成基于原始的5'- 烯丙基磷酸尿苷与1,4 - 二脱氧 - 1,4 - 亚氨基半乳糖醇衍生的环硝酮的高度区域和立体选择性环加成反应，随后对环加成产物进行还原修饰。所得的亚氨基半乳糖 - UMP共轭物是新型的糖核苷酸模拟物，可用作UDP - Gal变位酶和UDP - Galf转移酶的抑制剂。