Multigram synthesis of an orthogonally-protected pentasaccharide for use as a glycan precursor in a Shigella flexneri 3a conjugate vaccine: application to a ready-for-conjugation decasaccharide
| Autor: | Marion Bouchet, Zhaoyu Hu, Laurence A. Mulard, Johan Cornil |
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| Přispěvatelé: | Chimie des Biomolécules - Chemistry of Biomolecules, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Institut Pasteur under grant agreement GPH-FLEXBIVAC (postdoctoral fellowship to J.C.) and by the European Union's seventh Framework Program for research, technological development, and demonstration under grant agreement no 261462-STOPENTERICS (postdoctoral fellowship to Z.H.)., The authors would like to acknowledge Ms Catherine Guerreiro (Chemistry of Biomolecules) for her excellent advice with regard to RP-HPLC. They also thank Mr Frederic Bonhomme (UMR3523 CNRS) for the HRMS spectra., European Project: 261472,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,STOPENTERICS(2010) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Glycan Glycosylation biology Glycoconjugate Dimer [SDV]Life Sciences [q-bio] Organic Chemistry biology.organism_classification Chemical synthesis Combinatorial chemistry chemistry.chemical_compound Shigella flexneri chemistry biology.protein Moiety [CHIM]Chemical Sciences Azide [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology |
| Zdroj: | Organic Chemistry Frontiers Organic Chemistry Frontiers, 2021, 8 (22), pp.6279-6299. ⟨10.1039/d1qo00761k⟩ |
| ISSN: | 2052-4129 |
| Popis: | International audience; 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 crystalline 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. |
| Databáze: | OpenAIRE |
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