Glycosyl triflates, which serve as important intermediates in glycosylation reactions, were generated and accumulated by low-temperature electrochemical oxidation of thioglycosides, such as thioglucosides, thiogalactosides, and thiomannosides, in the presence of tetrabutylammonium triflate (Bu4NOTf) as a supporting electrolyte. The solutions of glycosyl triflates thus obtained were then characterized by low-temperature NMR measurements. The thermal stability of glycosyl triflates and their reactions with glycosyl acceptors were also studied.
Despite advances in synthetic carbohydrate chemistry, the 1,2-cis-selective glycosylation reaction of 2-deoxy-2-amino sugars has not progressed during the last three decades. For such glycosylations, 2-azide glycosyl donors have been extensively employed, notwithstanding difficulties in their preparation and moderate selectivities. Herein, we report on a highly 1,2-cis-selective trans-carbamate sugar donor, which can be readily prepared in high yields. Furthermore, the utility of the novel cis-selective glycosyl donor for preparing complex oligosaccharides is demonstrated through the effective synthesis of an anti-Helicobacter pylori hexasaccharide.
For the preparation of both N-linked and O-linked sialylglycopeptides and their glycoprotein form, the critical points in these syntheses are the preparation of an appropriate amount of sialyloligosaccharyl-amino acid and isolation of the sialylglycopeptides. In particular, it have been difficult to isolate O-linked sialylglycopeptides in which the sialyl linkage is labile to acid treatment and the N-acetyl-galactosaminyl linkage is labile to base-treatment. For the preparation of target glycoproteins by the use of such sialylglycopeptide thus obtained, an efficient coupling method should be essential. In this review, we introduce our new sialyl donors for the synthesis of sialyl-TN epitope and O-linked sialyl-TN-glycopeptides, and a new concept for a glycopeptide coupling reaction in the synthesis of glycoproteins.
The ErbB2/ErbB3 heterodimer elicits potent mitogenic and transforming signals, and clinical studies indicate that these receptors play an important role in tumor incidence and progression. In this study, a series of human ErbB3 mutants devoid of N-glycans expressed in Flp-In-CHO cells were used to determine whether N-glycosylation is involved in the function of ErbB3. A crosslinking study showed that the Asn418 to Gln mutant (N418Q) of ErbB3 underwent heregulin (HRG)-independent autodimerization. Furthermore, ErbB3-N418Q autodimerized with ErbB2 in the absence of HRG, and receptor tyrosine phosphorylation and subsequent extracellular signal-regulated kinase (ERK) and Akt phosphorylation were promoted. A cell proliferation assay and a soft agar colony formation assay demonstrated that ErbB2/ErbB3-N418Q co-expression promoted cell proliferation and colony formation in soft agar in ERK- and Akt-dependent manners. ErbB2/ErbB3-N418Q co-expression also promoted the growth of tumors in athymic nude mice when injected subcutaneously. These results suggest that the Asn418-linked N-glycan in ErbB3 plays a crucial role in regulating receptor dimer formation and transforming activity.