Chemical Synthesis of a Branched Nonasaccharide Fragment from <i>Helicobacter pylori</i> Lipopolysaccharide
Ling Li, Xiao-Chen Yin, Yuanyuan Jiang, Yi-Fei Xia, Xia Wang, Jiao Li, Hong Li, Yong Qin, Jin‐Song Yang
Abstract
A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include the highly stereoselective construction of β-3-deoxy- d - manno -oct-2-ulosonic acid (Kdo) and two 1,2- cis -glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired β-Kdo glycoside and 1,2- cis -α- l -fucoside/ d -glucoside. Moreover, the key branched framework was successfully established through a [(7 + 1) + 1] assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.