1,3-syn-Diaxial Repulsion of Typical Protecting Groups Used in Carbohydrate Chemistry in 3-O-Substituted Derivatives of Isopropyl d-Idopyranosides

Abstract

The strength of 1,3-syn-diaxial repulsion was evaluated for main types of protecting groups (alkyl, silyl, and acyl) usually used in carbohydrate chemistry. As molecular probes for this study, derivatives of isopropyl 2-O-benzyl-4,6-O-benzylidene-α-d-idopyranoside bearing allyl, acetyl, and tert-butyldiphenylsilyl (TBDPS) protecting groups at O-3 were prepared from p-methoxyphenyl d-galactopyranoside. The equilibrium between S and C conformations in these compounds was investigated using J and J coupling constants that were determined from 1D H NMR and 2D J-resolved HMBC spectra in various solvents. The analysis of the corresponding coupling constants calculated using DFT/B3LYP/pcJ-1 approximation applied to conformations optimized at DFT/B3LYP/6-311++G** level supported the investigation. Proportions of conformers in the equilibrium revealed the highest repulsion between the 3-allyloxy group and the isopropoxy aglycon and its dependence on the solvent polarity. Differences in the conformational behavior of 3-O-allyl and 3-O-acetyl-α-d-idopyranoside derivatives complied with the notion that higher electron density on O-3 increased 1,3-syn-diaxial repulsion. 3-O-TBDPS derivative existed mainly inC conformation. The attenuation of the 1,3-syn-diaxial repulsive interaction indicates that TBDPS has stereoelectronic properties that may have significance in context of fixing unnatural pyranoside conformation with the help of silyl groups but have been disregarded until now.

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

“…Changes in the conformations of monosaccharides expectedly accompany their modification with different functional groups. Thus, spatial repulsion of silyl groups results in inversion or distortion of the pyranoside ring [1–2], which strongly modifies the chemical behaviour of the pyranoside substrate by influencing the spatial environment of the reaction center and changing stereoelectronic effects [3–5]. A rather complex case is observed for sulfate groups; in addition to van der Waals interactions their negative charges contribute to the electrostatic forces.…”

Computational and NMR Conformational Analysis of Galactofuranoside Cycles Presented in Bacterial and Fungal Polysaccharide Antigens

“…This effect is also encountered in pyranosides. For example, in the work by (Komarova et al, 2017), we observed that this effect can cause conformational interchanges in idopyranosides. Presumably, in furanosides, it may influence to a larger extent since these molecules are not as conformationally rigid as pyranosides.…”

Chemical Synthesis and Application of Biotinylated Oligo-α-(1 → 3)-d-Glucosides To Study the Antibody and Cytokine Response against the Cell Wall α-(1 → 3)-d-Glucan of Aspergillus fumigatus

“…The main problem in the assembly of oligoglucoside chains of this type is the 1,2- cis stereoselectivity in the synthesis of α-glucosides, which is known to be a nontrivial task . To develop new methods for 1,2- cis -selective glycosylations, we have been constantly investigating the effect of stereoelectronic properties and other electronic interactions of protecting groups on the stereochemistry of the glycosylation, − and in particular, we have studied the possibility of remote anchimeric assistance. To achieve this goal, the use of the corresponding 6- O- benzoylated glycosylating agents was explored.…”

“…The filtrate was washed with saturated aqueous NaHCO 3 and water, the organic layer was separated, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (light (9). Heptasaccharide 8 (29 mg, 0.0069 mmol) was dissolved in 0.5 mL of a 1 M solution of hydrazine hydrate in pyridine−acetic acid (3:2).…”