Link to DOI – 10.1039/d1qo00761k
The rapidly growing interest in carbohydrate-based bioactive molecules calls for strategies enabling the
appropriate design and large-scale delivery of the glycan moiety. Herein, we describe the robust and
high-yielding chemical synthesis of an orthogonally-protected pentasaccharide intended for use as a
central building block in vaccine development against Shigella flexneri 3a. Elaborated from advanced crys-
talline intermediates and fine-tuned catalytic processes facilitating regio- and stereoselective conversions,
a robust [2 + 3] strategy was designed, which avoided several tedious purifications and efficiently delivered
multigram amounts of the target pentasaccharide. Conversion of this intermediate into a donor and a
linker-equipped acceptor then merging then into the frame of a [5 + 5] glycosylation step furnished a
decasaccharide encompassing one trichloroacetamide moiety per repeat. Chemoselective delevulination
and subsequent Pd(OH)2 -mediated hydrogenolysis enabling concomitant hydrodechlorination and azide
reduction gave the ready-for-conjugation dimer of the repeating unit of the O-antigen from S. flexneri 3a
featuring the natural stoichiometric O-acetylation. The proof-of-concept was established, opening the
way to larger S. flexneri 3a oligosaccharides and fine-tuned glycoconjugates.