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

The strength of 1,3-<i>syn</i>-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-<i>O</i>-benzyl-4,6-<i>O</i>-benzylidene-α-d-idopyranoside bearing allyl, acetyl, and <i>tert</i>-butyldiphenylsilyl (TBDPS) protecting groups at O-3 were prepared from <i>p</i>-methoxyphenyl d-galactopyranoside. The equilibrium between ^<i>O</i><i>S</i>₂ and ⁴<i>C</i>₁ conformations in these compounds was investigated using ³<i>J</i>_H,H and ³<i>J</i>_C,H coupling constants that were determined from 1D ¹H NMR and 2D <i>J</i>-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-<i>O</i>-allyl and 3-<i>O</i>-acetyl-α-d-idopyranoside derivatives complied with the notion that higher electron density on O-3 increased 1,3-<i>syn</i>-diaxial repulsion. 3-<i>O</i>-TBDPS derivative existed mainly in ⁴<i>C</i>₁ conformation. The attenuation of the 1,3-<i>syn</i>-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

Combination of 3‑<i>O</i>‑Levulinoyl and 6‑<i>O</i>‑Trifluorobenzoyl Groups Ensures α‑Selectivity in Glucosylations: Synthesis of the Oligosaccharides Related to <i>Aspergillus fumigatus</i> α‑(1 → 3)‑d‑Glucan

Stereospecific α-glucosylation of primary and secondary OH-group at carbohydrate acceptors is achieved using glucosyl N-phenyl-trifluoroacetimidate (PTFAI) donor protected with an electron-withdrawing 2,4,5-trifluorobenzoyl (TFB) group at O-6 and the participating levulinoyl (Lev) group at O-3. New factors have been revealed that might explain α-stereoselectivity in the case of TFB and pentafluorobenzoyl (PFB) groups at O-6. They are of conformational nature and confirmed by DFT calculations. The potential of this donor, as well as the orthogonality of TFB and Lev protecting groups, is showcased by the synthesis of α-(1 → 3)-linked pentaglucoside corresponding to Aspergillus fumigatus α-(1 → 3)-d-glucan and of its hexasaccharide derivative, bearing β-glucosamine residue at the non-reducing end