Synthetic Zwitterionic Streptococcus pneumoniae Type 1 Oligosaccharides Carrying Labile O‐Acetyl Esters

Angewandte Chemie International Edition, vol. 62, pp. e202211940

Abstract

We herein report the first total synthesis of the Streptococcus pneumoniae serotype 1 (Sp1) oligosaccharide, a unique zwitterionic capsular polysaccharide carrying labile O-acetyl esters. The target oligosaccharides, featuring rare α-2,4-diamino-2,4,6-trideoxy galactose (AAT) and α-galacturonic acids, were assembled up to the 9-mer level, in a highly stereoselective manner using trisaccharide building blocks. The lability of the O-acetyl esters imposed a careful deprotection scheme to prevent migration and hydrolysis. The migration was investigated in detail at various pD values using NMR spectroscopy, to show that migration and hydrolysis of the C-3-O-acetyl esters readily takes place under neutral conditions. Structural investigation showed the oligomers to adopt a right-handed helical structure with the acetyl esters exposed on the periphery of the helix in close proximity of the neighboring AAT residues, thereby imposing conformational restrictions on the AATα1-4GalA(3OAc) glycosidic linkages, supporting the helical shape of the polysaccharide, that has been proposed to be critical for its unique biological activity.

Authors 8

1. Zhen Wang Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden (The Netherlands

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden (The, Netherlands

2. Ana Gimeno

   CIC bioGUNE

   Affiliation as printed

   CIC bioGUNE Bizkaia Technology Park, Building 801A 48170 Derio Spain

   CIC bioGUNE, Bizkaia Technology Park, Building 801A, 48170 Derio, Spain

3. Marta G. Lete

   CIC bioGUNE

   Affiliation as printed

   CIC bioGUNE Bizkaia Technology Park, Building 801A 48170 Derio Spain

   CIC bioGUNE, Bizkaia Technology Park, Building 801A, 48170 Derio, Spain

4. Herman S. Overkleeft Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden (The Netherlands

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden (The, Netherlands

5. Gijsbert A. van der Marel Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden (The Netherlands

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden (The, Netherlands

6. Fabrizio Chiodo

   Istituto di Chimica Biomolecolare · National Research Council · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Amsterdam Infection and Immunity Institute Department of Molecular Cell Biology and Immunology Amsterdam UMC, Location VUmc 1007 MB Amsterdam (The Netherlands

   Institute of Biomolecular Chemistry National Research Council (CNR) Pozzuoli, Napoli Italy

   Amsterdam Infection and Immunity Institute, Department of Molecular Cell Biology and Immunology Amsterdam UMC, Location VUmc, 1007 MB Amsterdam (The, Netherlands

   Institute of Biomolecular Chemistry, National Research Council (CNR), Pozzuoli, Napoli, Italy

7. Jesús Jiménez‐Barbero

   Ikerbasque · University of the Basque Country · Centro de Investigación Biomédica en Red de Enfermedades Respiratorias · CIC bioGUNE

   Affiliation as printed

   CIC bioGUNE Bizkaia Technology Park, Building 801A 48170 Derio Spain

   Centro de Investigación Biomédica En Red de Enfermedades Respiratorias Madrid Spain

   Department of Organic Chemistry II Faculty of Science and Technology, EHU-UPV 48940 Leioa Spain

   Ikerbasque Basque Foundation for Science Plaza Euskadi 5 48009 Bilbao, Bizkaia Spain

   CIC bioGUNE, Bizkaia Technology Park, Building 801A, 48170 Derio, Spain

   Department of Organic Chemistry, II Faculty of Science and Technology, EHU-UPV, 48940 Leioa, Spain

   Ikerbasque, Basque Foundation for Science, Plaza Euskadi 5, 48009 Bilbao, Bizkaia, Spain

8. Jeroen D. C. Codée corresponding Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden (The Netherlands

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden (The, Netherlands