O-Glycosylation Enabled by N-(Glycosyloxy)acetamides

Abstract

A novel glycosylation protocol has been established by using N-(glycosyloxy)acetamides as glycosyl donors. The N-oxyacetamide leaving group in donors could be rapidly activated in the presence of Cu(OTf) or SnCl under microwave irradiation. This glycosylation process afforded the coupled products in high yields, and the reaction enjoyed a broad substrate scope, even for disarmed donors and hindered acceptors. The easy availability of the donors, the high stability of N-(glycosyloxy)acetamides, and the small leaving group make this method very practical.

Efficient and versatile formation of glycosidic bonds via catalytic strain-release glycosylation with glycosyl ortho−2,2-dimethoxycarbonylcyclopropylbenzoate donors

“…However, under our conditions, the two glycosylation reactions proceeded smoothly to deliver the corresponding O −2 and O −4 linked disaccharides 3k and 3 l in 89% and 91% under very mild conditions. N -Hydroxylphthalimide 2 m and ortho -iodobenzoic acid 2n were good coupling partners to glycosylate with 1a to afford the intended glycosides, which are latent forms of N -(glycosyloxy)acetamides 61 and ortho -alkynylbenzoates, showcasing the versatility and flexibility of the strain-release glycosylation. It should also be noted that the previous preparation of aminooxy glycoside 3 m entailed unstable glycosyl halides in the presence of stoichiometric silver salt or propargyl 1,2-orthoesters with a gold catalyst to give the products in only moderate yields 61 , 62 .…”

“…N -Hydroxylphthalimide 2 m and ortho -iodobenzoic acid 2n were good coupling partners to glycosylate with 1a to afford the intended glycosides, which are latent forms of N -(glycosyloxy)acetamides 61 and ortho -alkynylbenzoates, showcasing the versatility and flexibility of the strain-release glycosylation. It should also be noted that the previous preparation of aminooxy glycoside 3 m entailed unstable glycosyl halides in the presence of stoichiometric silver salt or propargyl 1,2-orthoesters with a gold catalyst to give the products in only moderate yields 61 , 62 . Our facile synthesis of 3 m gave an example of the catalytically feasible method using cheap rare earth metal as the catalyst, which could supply potentially easier access to various aminooxy glycosides of biological interests like calicheamicin 63 and artificial glycopeptides 64 .…”

The impact of N-glycans on the immune response of plant-produced SARS-CoV-2 RBD-Fc proteins

“…It is crucial for the proper conformation, functionality, and stability of both membrane-bound and soluble glycoproteins. This process is initiated in the endoplasmic reticulum (ER) and undergoes successive glycan processing in the Golgi apparatus [ 18 ]. Glycosylation can be categorized into two main types: N-glycosylation and O-glycosylation.…”