Synthesis and modification of spacered glycosides of N-acetylglucosamine

Abstract

From glucosaminyl chloride peracetate, in the presence of HgI 2, we have obtained fl-p-nitrobenzyl-, fl-o~-chloro-and fl-w-azido-spacered glycosides of N-acetylglucosamine (NAG) [7] protection; and also o~-azidoalkyl glycosides [8]. In recent years, great interest has been aroused by w-halogenoalkyl glycosides, which are easily modified to form oJ-carboxy and oJ-amino derivatives or glycolipids [9].As catalyst in the synthesis of glycosides of N-acetylglucosamine (NAG)glycosides, we propose HgI 2, which permits the use of a readily obtainable and stable glycosyl donor --the a-chloride (1) [10]. Our aim was to develop a convenient method of synthesizing oJ-chloro-and oJ-amino-spacered glycosides of NAG with spacers of different chemical natures, and their modification.The glycosylation of p-nitrobenzyl alcohol with the ,~-chloride (1) was carried out at room temperature in dichloroethane in the presence of mercury(II) iodide and molecular sieves 3. The ~-p-nitrobenzyl glycoside (2) was obtained by crystallization with a yield of 52 %. Its structure was confirmed by its PMR spectrum, in which we identified signals from the protons of the carbohydrate residue (see the Experimental part) and the aglyeon: two doublets of an AB-system of methylene protons with CSs of 4.70 and 5.02 ppm and twJo doublets of aromatic protons with CSs of 7.48 and 8.20 ppm. The 8-configuration of the glycosidic bond followed from the presence in the spectrum of the doublet of the anomeric proton with a CS of 4.76 ppm and the SSCC 8.5 Hz. The nitro group in compound (2) was subjected to hydrogenation over a platinum catalyst, and the amine (3) obtained was converted by the action of 2-dodeeyltetradecanoic acid into the lipophilie derivative (4). AS compared with that of compound (2), its PMR spectrum contained an additional triplet with a CS of 0.88 ppm from two terminal methyl groups and an intense multiplet of methylene protons with a CS of 1.24 ppm, which confirmed the introduction of the lipophilic component.Analogously, the interaction of 4-chlorobutyl and 6-chlorohexyl alcohols with the a-chloride (1) gave the chloroglycosides (Sa, b), which we had obtained previously by an oxazoline synthesis [8]. The treatment of chlorine derivatives (Sa, b) with sodium azide in the presence of tetraethylammonium bromide led to the oJ-azidoalkyl glycosides (6a, b). The PMR spectrum of compound (6a) included a triplet with the CS 3.23 ppm of a oJ-methylene group, two multiplets with CSs of 3.49 and 3.81 ppm of nonequivalent protons of an a-methylene group, and two multiplets with CSs of 1.18 and 1.59 ppm for the other CH 2 groups (see the Experimental part). The Zemplen deacetylation of glycoside (6a), followed by reduction of the azido function, led to the amine (8a), from which, by the method of [11], we obtained a conjugate of B-N-acetylglucosamine with polyacrylamide. Such conjugates earl be used for typing lectins or antibodies [12].

Mechanistic Insight into Nanomolar Binding of Multivalent Neoglycopeptides to Wheat Germ Agglutinin

“…Enzyme linked lectin assay : Assays were carried out as previously described using a different linker for coating of the microtiter plates. Briefly, microtiter plates with covalently immobilized reference ligand 11‐amino‐3,6,9‐trioxaundecyl 2‐acetamido‐2‐deoxy‐β‐ d ‐glucopyranoside were incubated with mixtures of horseradish peroxidase (HRP)‐labeled WGA (1 μg mL −1 ) and the respective WGA ligand in varying concentrations. After incubation, the plates were washed and remaining labeled WGA bound to the reference ligand was quantified by an HRP‐catalyzed color reaction using 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS) as substrate.…”

Glycosylation: The Direct Synthesis of 2‐Acetamido‐2‐Deoxy‐Sugar Glycosides

“…Activation of chloride 9a was also studied using mercury(II) iodide as shown with the example of the GlcNAc acceptor 50 , leading regioselectively to the β‐(1–6)‐disaccharide 52 after acetylation with an overall yield of 65 % (Scheme ) …”