Methodology Development and Physical Organic Chemistry: A Powerful Combination for the Advancement of Glycochemistry

Abstract

This perspective article outlines work in the Crich group on the diastereoselective synthesis of the so-called difficult classes of glycosidic bond; the 2-deoxy-β-glycopyranosides, the β-mannopyranosides, the α-sialosides, the α-glucopyranosides and the β-arabinofuranosides with an emphasis on the critical interplay between mechanism and methodology development.

Chemical approach for the syntheses of GM4 isomers with sialic acid to non-natural linkage positions on galactose

“…The influence of the solvent on the sialylation was probably due to both the moderate solvent polarity and stabilization of the oxocarbenium ion due to the nitrile effect. [28][29][30] This same solvent-system was applied to following sialylations. Next, the effect of acceptors with acyl and alkyl protecting groups on the sialylation was investigated using synthesized a(2?6) and a(2?3) linked GM4 derivatives ( Table 2).…”

“…The 3 J C1,H-3ax coupling constants were measured by the phase-sensitive gradient-enhanced HMBC spectra. 30,36 Multiplicities are reported by using the following abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad; J = coupling constant values in Hertz. Mass spectra (MS) and high-resolution mass spectra (HRMS) were recorded with a JEOL JMS-S3000 mass spectrometer using 2,5-dihydroxybenzoic acid (DHBA) as the matrix.…”

Automated Chemical Synthesis of Oligosaccharides and Glycoconjugates

“…This reactions proceeded regioselectively at the C-4 position, and the resulting pentasaccharide equipped with the anomeric thiophenyl leaving group was used as the glycosyl donor for the coupling with the glycosyl acceptor (46), which was added along with NIS/TfOH to affect the activation. Finally, the remaining 3′-OH of the resulting hexasaccharide intermediate was fucosylated by the addition of a donor (47) and NIS/TfOH. Resultantly, the desired heptasaccharide (48) was obtained in eight hours in 24% yield (average 79% yield per step).…”

Significant Substituent Effect on the Anomerization of Pyranosides: Mechanism of Anomerization and Synthesis of a 1,2‐cis Glucosamine Oligomer from the 1,2‐trans Anomer

“…Hence, chemical synthesis of oligosaccharides would be an extremely useful com-plementary approach to produce homogeneous and well-defined substances. The chemical synthesis of glycosides has contributed greatly to glycobiology and glycotechnology; [4][5][6][7][8][9][10] in particular, the glycosylation reaction is recognized as one of the most essential reactions in oligosaccharide synthesis. This reaction, which involves the formation of a glycosidic linkage between a sugar donor and a glycosyl acceptor, has seen remarkable developments in recent times with respect to the wealth of synthetic methods available.…”