title: Origin of problems related to Staudinger reduction in carbopeptoid syntheses.
abstract: We report the solid phase synthesis of -GG-X-GG- type α/β-carbopeptoids incorporating RibAFU(ip) (1a, tX) or XylAFU(ip) (2a, cX) sugar amino acids. Though coupling efficacy is moderate, both the lengthier synthetic route using Fmoc derivative (e.g., Fmoc-RibAFU(ip)-OH) and the azido derivative (e.g., N3-RibAFU(ip)-OH) via Staudinger reaction with nBu3P can be successfully applied. Both X-ray diffraction,1H- and31P-NMR, and theoretical (QM) data support and explain why the application of Ph3P as Staudinger reagent is "ineffective" in the case of a cis stereoisomer, if cX is attached to the preceding residue with a peptide (-CONH-) bond. The failure of the polypeptide chain elongation with N3-cX originates from the "coincidence" of a steric crowdedness and an electronic effect disabling the mandatory nucleophilic attack during the hydrolysis of a quasi penta-coordinated triphenylphosphinimine. Nevertheless, the synthesis of the above α/β-chimera peptides as completed now by a new pathway via 1,2-O-isopropylidene-3-azido-3-deoxy-ribo- and -xylo-furanuronic acid (H-RibAFU(ip)-OH 1a and H-XylAFU(ip)-OH 2a) coupled with N-protected α-amino acids on solid phase could serve as useful examples and starting points of further synthetic efforts.
authors.affiliation: Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter s. 1/A, Budapest, 1117, Hungary.
authors.forename: Barbara
authors.initials: B
authors.lastname: Csordás
authors.affiliation: Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter s. 1/A, Budapest, 1117, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Nagy
authors.affiliation: Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter s. 1/A, Budapest, 1117, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Harmat
authors.affiliation: MTA-ELTE Protein Modelling Research Group, Pázmány Péter s. 1/A, Budapest, 1117, Hungary.
authors.forename: Virág
authors.initials: V
authors.lastname: Zsoldos-Mády
authors.affiliation: BME Department of Applied Biotechnology and Food Science, Szent Gellért tér 4, Budapest, 1111, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Leveles
authors.affiliation: Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter s. 1/A, Budapest, 1117, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Pintér
authors.affiliation: MTA-ELTE Protein Modelling Research Group, Pázmány Péter s. 1/A, Budapest, 1117, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Farkas
authors.affiliation: Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter s. 1/A, Budapest, 1117, Hungary. perczel@chem.elte.hu.|MTA-ELTE Protein Modelling Research Group, Pázmány Péter s. 1/A, Budapest, 1117, Hungary. perczel@chem.elte.hu.
authors.forename: András
authors.initials: A
authors.lastname: Perczel
mesh_terms: D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D006020:Glycopeptides
keywords: Carbopeptoids; Iminophosphorane; Staudinger reaction; Sugar amino acids