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Exploring the Effect of Bioisosteric Replacement of Carboxamide by a Sulfonamide Moiety on N ‐Glycosidic Torsions and Molecular Assembly: Synthesis and X‐ray Crystallographic Investigation of N ‐(β‐ D ‐Glycosyl)sulfonamides as N ‐Glycoprotein Linkage Region Analogues
Author(s) -
Srivastava Amrita,
Varghese Babu,
Loganathan Duraikkannu
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201302018
Subject(s) - glycosidic bond , chemistry , moiety , stereochemistry , intramolecular force , glycosyl , dihedral angle , hydrogen bond , crystal structure , crystallography , molecule , biochemistry , organic chemistry , enzyme
N ‐Glycoprotein linkage region constituents, 2‐acetamido‐2‐deoxy‐β‐ D ‐glucopyranose (GlcNAc) and asparagine (Asn) are conserved among all the eukaryotes. To gain a better understanding for nature’s choice of GlcNAcβAsn as linkage region constituents and inter‐ and intramolecular carbohydrate–protein interactions, a detailed systemic structural study of the linkage region conformation is essential. Earlier crystallographic studies of several N ‐(β‐glycopyranosyl)alkanamides showed that N ‐glycosidic torsion, ϕ N , is influenced to a larger extent by structural variation in the sugar part than that of the aglycon moiety. To explore the effect of the bioisosteric replacement of a carboxamide group by a sulfonamide moiety on the N ‐glycosidic torsions as well as on molecular assembly, several glycosyl methanesulfonamides and glycosyl chloromethanesulfonamides were synthesized as analogues of the N ‐glycoprotein linkage region, and crystal structures of seven of these compounds have been solved. A comparative analysis of this series of crystal structures as well as with those of the corresponding alkanamido derivatives revealed that N ‐glycosidic torsion, ϕ N, does not alter significantly. Methanesulfonamido and chloromethanesulfonamido derivatives of GlcNAc display a different aglycon conformation compared to other sulfonamido analogues. This may be due to the cumulative effect of the direct hydrogen bonding between N1 and O1′ and CH⋅⋅⋅O interactions of the aglycon chain, revealing the uniqueness of the GlcNAc as the linkage sugar.