Glycoproteins play a key role in a multitude of biological events in living organisms. Hence, neoglycopeptides obtained from unnatural C-glycosyl alpha-amino acids can be used as synthetic probes in studies aiming at clarifying the role of the carbohydrate domain in glycoprotein biological activity. A new class of C-glycosyl alpha-amino acids featuring a nitrogenated heterocycle ring holding the carbohydrate and glycinyl moiety was designed in our laboratory. Having previously prepared isoxazole-, 1,2,3-triazole-, and pyridine-tethered compounds, the family has now been enlarged by a group of newcomers represented by tetrazole derivatives. Two sets of compounds have been prepared, one being constituted of C-galactosyl and C-ribosyl O-tetrazolyl serines while the other contains S-tetrazolyl cysteine derivatives. In both cases, the synthetic scheme involved a two-step route, the first one being the thermal cycloaddition of a sugar azide with p-toluensulfonyl cyanide (TsCN) to give a 1-substituted 5-sulfonyl tetrazole and the second the replacement of the tosyl group with a serine or cysteine residue. For the high efficiency and operational simplicity, the azide-TsCN cycloaddition appears to be a true click process. Finally, one of the amino acids prepared was incorporated into a tripeptide.

C-Glycosylmethyl pyridylalanines reported in this paper constitute a novel family of glycosyl amino acids that contain a pyridine ring linking the carbohydrate and amino acid residues. These amino acids may serve to prepare nonnatural glycopeptides displaying firmly bound carbohydrate fragments through a rigid and highly stable tether. A viable route to these new hybrid molecules has been opened via thermally induced Hantzsch-type cyclocondensation using an aldehyde-ketoester-enamino ester system. To one of these reagents was attached a C-glycosyl residue, while to another was bound an amino acid fragment. In a one-pot optimized methodology, the dihydropyridine was not isolated while its purification was carried out by removal of unreacted material and side products using polymer-supported scavengers. Then the dihydropyridine (mixture of diastereoisomers) was oxidized by a polymer-bound oxidant to give the target pyridine bearing the two bioactive residues. In this way a range of eight compounds (58-68% yield) was prepared in which the elements of diversity were (i) the gluco and galacto configurations of the pyranose ring, (ii) the alpha- and beta-configurations at the anomeric center, and (iii) the positions of the carbohydrate and amino acid sectors in the pyridine ring. The orthogonal functional group protection in these amino acids allowed their easy incorporation into oligopeptides via sequential amino and carboxylic group coupling.

The nickel and palladium catalyzed Kumada-Tamao-Corriu cross-coupling reaction is a powerful method for the formation of carbon-carbon bonds, employed in many large-scale applications in the pharmaceutical and electronic material industries. Kumada cross-coupling is the reaction of an organohalide substrate with a Grignard reagent to produce the corresponding coupled product using a palladium or nickel catalyst. This review covers key developments in Kumada cross-coupling reactions over the past ten years.

Amino acids U 0400Click Azide-Nitrile Cycloaddition as a New Ligation Tool for the Synthesis of Tetrazole-Tethered C-Glycosyl α-Amino Acids. -(ALDHOUN, M.; MASSI*, A.; DONDONI, A.; J. Org. Chem. 73 (2008) 24, 9565-9575; Dip. Chim., Univ. Ferrara, I-44100 Ferrara, Italy; Eng.) -Jannicke 16-189

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