Efficient Synthesis of Antigenic Trisaccharides Containing N‐Acetylglucosamine: Protection of NHAc as NAc₂

Abstract

The antigenic trisaccharides, α‐gal epitope and H antigen, containing N‐acetyl‐d‐glucosamine (GlcNAc) were synthesized using a diacetyl strategy, in which NHAc is tentatively converted to NAc2 during oligosaccharide construction. Acetylation of NHAc in GlcNAc significantly improved the reactivity in glycosylation reactions. The diacetyl strategy allowed to achieve the efficient synthesis of α‐gal through a sequential one‐pot and one‐flow procedure. Meanwhile, H antigen was synthesized by stepwise elongation from the reducing end side of GlcNAc. The enhancement of the reactivity by NAc2 protection was observed in both glycosylations at proximal and distal positions to GlcNAc. This diacetyl strategy is expected to be applicable to the synthesis of a wide range of glycans.

Exploratory N‐Protecting Group Manipulation for the Total Synthesis of Zwitterionic Shigella sonnei Oligosaccharides

“…In line with previous achievements in the synthesis of neuraminic acid containing oligosaccharides, [59] the masking of the acetamide moiety of glucosamine in the form of the corresponding bis ‐acetylated imide was adopted successfully on several occasions, [57, 58b, 60] including in the synthesis of an undecasaccharide featuring a Kdo 2 GlcNAc 2 backbone [58d] . The acetamido function is readily recovered upon treatment of the elongated intermediate under mild alkaline conditions, most often Zemplén conditions, [58b] without any manipulation of the amine.…”

Synthesis of ABO blood group antigens and functional glycan display on the cell surface

“…Synthesis of H antigen 16 is shown in Scheme 2. Compound 10, reported previously by our group, 35 was converted to a galactosyl donor 1. Selective cleavage of benzylidene 36 followed by benzoyl protection generated 1.…”

Recent Chemical and Chemoenzymatic Strategies to Complex-Type N-Glycans

“…The stereoselective construction of β-D-mannosidic bonds has always been a hot topic as one of the most difficult issues in glycochemistry (Tsutsui et al, 2020;Ding et al, 2018;Zhong et al, 2021). Stereo electronic effects such as the anomeric effect and C (2)-OH axial substitution of mannose is both beneficial to the formation of α-configuration products.…”

“…The strategy was applied to the synthesis of H antigen trisaccharide (Manabe, 2020) as well as 3-and 6-αsialylated tetraantennary N-glycans for H1N1 neuraminidase recognition (Manabe, 2021) very recently (Figure 6).…”