Click azide-nitrile cycloaddition as a new ligation tool for the synthesis of tetrazole-tethered C-glycosyl alpha-amino acids.
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.
Aldhoun
Mohammad
M
Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, Via L. Borsari 46, I-44100 Ferrara, Italy.
Massi
Alessandro
A
Dondoni
Alessandro
A
D000596:Amino Acids / Q000138:chemical synthesis*; D001386:Azides / Q000138:chemical synthesis*; D003500:Cyclization; D003545:Cysteine / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009570:Nitriles / Q000138:chemical synthesis*; D009842:Oligopeptides / Q000138:chemical synthesis; D013777:Tetrazoles / Q000138:chemical synthesis*
D000596:Amino Acids; D001386:Azides; D006023:Glycoproteins; D007202:Indicators and Reagents; D009570:Nitriles; D009842:Oligopeptides; D013777:Tetrazoles; D003545:Cysteine