Solid-Phase Synthesis of Thioether-Linked Glycopeptide Mimics for Application to Glycoprotein Semisynthesis

Abstract

[reaction: see text]. Glycoproteins are particularly suited to protein semisynthesis since homogeneous samples for biological analyses are not readily available using traditional recombinant techniques. Here we apply glycosyl iodoacetamides, normally used for the modification of bacterially derived proteins, to solid-phase glycopeptide synthesis. This provides access to glycopeptide alpha-thioesters, which may lend themselves to the semisynthesis of homogeneous N-linked glycoprotein mimics and novel glycopeptide libraries.

Characterizing non-hydrolyzing Neisseria meningitidis serogroup A UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase using UDP-N-acetylmannosamine (UDP-ManNAc) and derivatives

“…44 Free GlcNAc was treated with acetyl chloride to prepare peracetylated glycosyl chloride B (2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-D-glucopyranosyl chloride) in 56% yield, 45 which was used for the formation of peracetylated glucal C (85% yield) by treating with isopropenyl acetate 44 in the presence of catalytic amount of p -toluenesulfonic acid ( p -TsOH). Deacetylation of C using sodium methoxide in methanol 46 removed the O-acetyl groups and one of the two N-acetyl groups to produce the desired product 2-acetamidoglucal D in a 96% yield.…”

Preparation of aminoethyl glycosides for glycoconjugation

“…The chemical conjugation of carbohydrates through the anomeric centre to biomolecules such as peptides, proteins, lipids, metabolites and to array surfaces is an important synthetic challenge [1–5]. A diverse range of linkers and spacers has been described in the literature [2–12], among which aminoalkyl glycosides have become the most popular, in particular the aminoethyl linker.…”

N-Bromoacetyl-β-D-glycopyranosylamines in the synthesis of glycoconjugates of nitrogen-containing physiologically active compounds

“…N,N Diisopropylethylamine (0.34 mL, 2 mmol) was added with stirring to a heterogeneous mixture of 2 acetamido N bromoacetyl 2 deoxy β D gluco pyranosylamine 8 (341 mg, 1 mmol) (1a) and nicotinic acid (2) (246 mg, 2 mmol) in MeOH (7 mL (5) 2 Acetamido N [(2 benzyl 1H benzimidazol 1 yl)acetyl] 2 deoxy β β β β β D glucopyranosylamine (9). A mixture of compound 1a (341 mg, 1 mmol) and 2 benzyl 1H benzimidazole (3) (416 mg, 2 mmol) in N methyl 2 pyrrolidone (2.5 mL) was kept at 36 °C for 40 h. The precipitate that formed was filtered off, washed with MeOH and diethyl ether, and dried.…”