Chemical Synthesis of the Trio-Containing Pentasaccharide Fragment From Helicobacter pylori Lipopolysaccharide

Helicobacter pylori is a Gram-negative pathogen that persistently inhabits the human gastric mucosa and infects over half of the world's population.The lipopolysaccharide (LPS) of H. pylori represents a promising target for developing effective glycoconjugate vaccines. Herein, we report the first chemical synthesis of the LPS-derived pentasaccharide fragment from H. pylori, accomplished via a linear [(1+(1+(1+(1+1))))] glycosylation strategy. High stereoselectivity in the formation of 1,2-cis-L-fucosyl and 1,2-cis-D-glucosyl linkages was achieved through remote participation effects of the O4-benzoyl and O6-levulinoyl protecting groups, respectively. N-Phenyl trifluoroacetimidate glycosyl donors demonstrated higher efficiency than thioglycoside donors in glycosylation reactions, while TBSOTf proved superior to TMSOTf as a promoter for low-reactivity hydroxyl acceptors. In addition, a series of di-, tri-, and tetrasaccharide fragments bearing an aminopropyl linker were synthesized, facilitating glycan microarray construction and in vivo immunological evaluation, and thereby accelerating the development of a synthetic glycoconjugate vaccine against H. pylori.