Synthetic Zwitterionic Streptococcus Pneumoniae Type 1 Oligosaccharides Carrying Labile O-Acetyl Esters

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2022 Nov 9

PMID 36350770

Authors

Zhen Wang

Ana Gimeno

Marta G Lete

Herman S Overkleeft

Gijsbert A van der Marel

Fabrizio Chiodo

Jesus Jimenez-Barbero

Jeroen D C Codee

Affiliations

Soon will be listed here.

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.

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

Wang Z, Gimeno A, Lete M, Overkleeft H, van der Marel G, Chiodo F Angew Chem Int Ed Engl. 2022; 62(1):e202211940.

PMID: 36350770 PMC: 10107948. DOI: 10.1002/anie.202211940.

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