Saccharide directed synthesis

A first synthesis of a saccharide-peptide hybrid in a directed synthesis was performed by Yoshimura et al. in 1976 [50], The CAA 51 was activated with cyclo-hexylcarbodiimide and linked to amino sugar 52 to result in dimer 53. This glucuronic acid amide was less soluble in water than the corresponding mannuronic acid derivative. Dimer 53 could be converted, after removal of the anomeric protecting group by hydrogenation, to the amide-linked alditol 54 (Scheme 8) by reduction with sodium borohydride. This publication was not followed up at the time until the interest in carbohydrate mimetics rose [51]. 

M. Sevilla, C. Sanchis, T. Valdes-Solis, E. Morallon, A.B. Fuertes, 2008, Direct Synthesis Of Graphitic Carbon Nanostructures From Saccharides And Their Use As Electrocatalytic Supports, Carbon, 46, 6, 931-939. 

Even if the main focus on the research activities were directed towards structural studies on carbohydrates of natural origin, the synthesis of model substances, deriva-tization of oligo- and poly-saccharides, oxidation, and reduction of carbohydrates, and identification of the products all were performed during this time. 

The second methodology involves direct introduction of glycosylated moieties onto a suitably functionalized meso-arylporphyrin scaffold, accessible from a natural source (protoporphyrin-IX) or by total synthesis. Several O-,133,145,146 S-,147 and N-glycoporphyrins148 (125-129) have thus been prepared (Fig. 12). Moreover, in order to explore the influence of the clustered peripheral saccharides around the porphyrin scaffolds, and to evaluate their photophysical properties, the synthesis of dodecavalent porphyrins bearing four trivalent glycodendrons via amide ligation (129) has been achieved.149... 

Table II (104) shows the results of an experiment to learn the proportion of a-D-glucosyl fluoride that is hydrolyzed vs. that used for saccharide synthesis by the different crystalline a-amylases and by diluted saliva. The substrate was again 0.2 M and the enzymes at one-tenth to one-one hundredth the concentrations of the preceding experiment. These digests were analyzed directly for amounts of fluoride (104, 107) and D-glucose (glucose oxidase method) liberated during 2 hours at 30°C.

A crucial step in the chemical synthesis of glycopeptides is the incorporation of the saccharide into the peptide. Two approaches can be considered to accomplish this the direct glycosylation of a properly protected full-length peptide and the use of a preformed glycosylated amino acid building block for the stepwise synthesis of the peptide backbone (Scheme 1). 

Methylenation of 58 with an excess of the Takai reagent and subsequent RCM with the second generation Grubbs catalyst 7 (35 mol%) gave an intermediate (bis)-C-glycal which was directly subjected to hydroboration by BH3 THF and subsequent oxidative work-up to afford the C-trisaccharide 60 in 49% yield over three steps (26). Although double RCM reactions are known (27), this was the first time it has been used in the context of C-saccharide synthesis. 

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