TY - JOUR
T1 - Synthetic Zwitterionic Streptococcus pneumoniae Type 1 Oligosaccharides Carrying Labile O-Acetyl Esters
AU - Wang, Zhen
AU - Gimeno, Ana
AU - Lete, Marta G.
AU - Overkleeft, Herman S.
AU - van der Marel, Gijsbert A.
AU - Chiodo, Fabrizio
AU - Jiménez-Barbero, Jesús
AU - Codée, Jeroen D. C.
N1 - Funding Information: This work was supported by the Chinese Scholarship Council (CSC grant to Z. Wang), the Netherlands Organisation for Scientific Research (NWO VICI VI.C.182.020 to J.D.C.C), the European Research Council (ERC‐2017‐AdG, project number 788143‐RE‐CGLYCA NMR to J.J.B.) and Agencia Estatal de Investigación (Spain), projects RTI2018‐094751‐B‐C21 and CIBERES, an initiative of Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Funding Information: This work was supported by the Chinese Scholarship Council (CSC grant to Z. Wang), the Netherlands Organisation for Scientific Research (NWO VICI VI.C.182.020 to J.D.C.C), the European Research Council (ERC-2017-AdG, project number 788143-RE-CGLYCA NMR to J.J.B.) and Agencia Estatal de Investigación (Spain), projects RTI2018-094751-B-C21 and CIBERES, an initiative of Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Publisher Copyright: © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
PY - 2023/1/2
Y1 - 2023/1/2
N2 - 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.
AB - 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.
KW - Acyl Migration
KW - Bacterial Oligosaccharides
KW - Glycosylation
KW - Helical Structure
KW - Stereoselectivity
UR - http://www.scopus.com/inward/record.url?scp=85143273069&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/anie.202211940
DO - https://doi.org/10.1002/anie.202211940
M3 - Article
C2 - 36350770
SN - 1433-7851
VL - 62
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 1
M1 - e202211940
ER -