title: An insight into the radical thiol/yne coupling: the emergence of arylalkyne-tagged sugars for the direct photoinduced glycosylation of cysteine-containing peptides.
abstract: An explorative study of the Thiol-Yne Coupling (TYC) reaction has been carried out using an aliphatic (1-octyne) and an aromatic alkyne (phenylacetylene) and two alkanethiols (methyl thioglycolate and N-acetyl-L-cysteine methyl ester). The outcomes of the TYC reactions strongly depend on the experimental conditions (e.g., temperature, solvent, and alkyne/thiol ratio), but these can be properly adjusted to achieve selective production of either mono- or bis-coupling products. With respect to 1-octyne, phenylacetylene undergoes notably easier radical hydrothiolation, further showing a notably higher aptitude for monohydrothiolation exclusive of bis-hydrothiolation. The overall findings were exploited in glycosylation of cysteine derivatives as well as of cysteine-containing peptides. A sugar featuring an arylacetylene moiety gave rise to a true click-reaction, that is, glycosylation of the tripeptide glutathione in its native form, by means of virtually equimolar amounts of reagents. This reaction was successfully applied, under physiological conditions, to a cysteine-containing nonapeptide with marked advantages over the analogous Thiol-Ene Coupling (TEC) derivatization. A TYC/TEC sequence affording bis-armed cysteine derivatives through dual functionalization of an alkynyl sugar was additionally devised.
authors.affiliation: Dipartimento di Chimica Organica A. Mangini, Università di Bologna, Viale Risorgimento 4, I-40136 Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Minozzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Monesi
authors.forename: Daniele
authors.initials: D
authors.lastname: Nanni
authors.forename: Piero
authors.initials: P
authors.lastname: Spagnolo
authors.forename: Nicola
authors.initials: N
authors.lastname: Marchetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Massi
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D003545:Cysteine / Q000138:chemical synthesis* / Q000737:chemistry*; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D010777:Photochemistry; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D006020:Glycopeptides; D007202:Indicators and Reagents; D010455:Peptides; D013438:Sulfhydryl Compounds; D003545:Cysteine