Evidence of robust participation by an equatorial 4-O group in glycosylation on a 2-azido-2-deoxy-glucopyranosyl donor

Abstract

Although there are numerous claims of remote group participation leading to the synthesis of the expected glycosides with improved anomeric geometry outcome in glycosylation, there is still a lack of enough strong evidence and this has led to a long-term debate, particularly for equatorial 4-O group participation. In this work, we were able to synthesize and isolate a stable seven-membered trichlorooxazepine ring bridging intermediate with a high yield by employing a 2-azido-2-deoxy-glucopyranosyl donor, which provides strong evidence to support the putative participation of the equatorial 4-O group in glycosylation.

SnCl4-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

“…NMR also showed no correlation with position C-2, but exhibited a correlation separated by three bonds with the quaternary carbon atom of the acetyl group in position O-7 (Figure 3). The anomeric configuration of the acetolysis products was identified by the coupling constant for the correlation C-1-C-2-C-3-H-3 ax ( = 1.6-2.2 Hz, see Supporting Information File 1) and indicated the β-anomer [12][13][14][15][16]. Moreover, the similar chemical shifts of positions H-3 eq and H-3 ax in the 1 H NMR spectra of α-sialosides 6, 21, and 25 became much more different for the ring-opening products 12, 22, and 26, again representative of the β-configuration.…”

“…The driving force for the formation of a 2,3-dehydro derivative 24 might have been attributed to the presence of a destabilizing electron-withdrawing carboxy group flanking atom C-2 and the lack of a participating auxiliary in position C-3 of 5. Glycal 24 is widely used for α-sialylation by utilizing neighboring group participation and site-selective fluorination at C-3 [12][13][14]41]. Moreover, it is the main precursor in the synthesis of inhibitors for N-acetylneuraminidases from different sources [42].…”

“…In turn, this retarded the ring-opening reaction. The anchimeric participation of the NHAc group in stabilizing the axial conformation of the sialyl cation could also have affected cleavage of the ring [12][13][14].…”

“…The most common glycosidic linkages of Neu5Ac in glycoconjugates are α(2→3) and α(2→6) to galactose, α(2→8) and α(2→9) in polysialic acids [2,3], fucosyl and galactosyl α(1→4) to Neu5Ac, and intramolecularly C-7-to-C-2-linked (via oxygen), forming 2,7-anhydro-Neu5Ac [4][5][6]. Owing to the substantial role of sialic acids in biological systems, numerous synthetic methods have been described in the literature [7][8][9][10][11][12][13][14][15][16]. 2,7-Anhydro-Neu5Ac is the main prebiotic, which is utilized as a sole carbon source for human gut commensal anaerobic bacterium and plays a key biological role in body fluids and secretion [17][18][19].…”

Fernpartizipation in Glykosylierungen von Galaktose‐Bausteinen: Direktnachweis durch kryogene Schwingungsspektroskopie

“…Hierbei werden die Schutzgruppen durch das stark saure Medium allerdings vollständig protoniert, sodass die Ergebnisse nicht direkt auf die Bedingungen der klassischen Zuckersynthese übertragen werden können . In einer anderen Studie wurden Nebenprodukte isoliert, die deutliche, aber indirekte Hinweise für Fernpartizipation durch Acetylester an der C4‐Position von Glykosyldonoren lieferten . Alternativ dazu können massenspektrometriebasierte Methoden verwendet werden, um reaktive Intermediate aus Glykosylierungen in der Gasphase zu charakterisieren .…”