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Title/Abstract/Keywords

SYNTHESIS OF C-GLYCOSYL AMINO ACIDS AS STABLE BUILDING BLOCKS FOR MODIFIED GLYCOPEPTIDE SYNTHESIS

ALDHOUN, MOHAMMAD MOUSA (2009) SYNTHESIS OF C-GLYCOSYL AMINO ACIDS AS STABLE BUILDING BLOCKS FOR MODIFIED GLYCOPEPTIDE SYNTHESIS. PhD Thesis , Università degli studi di Ferrara.

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    Abstract

    In this thesis, we have studied and synthesized new class of C-glycosly amino acids whose structure features a hetrocycle ring holding the carbohydrate and the amino acid fragments. Pyridine and tetrazole rings were used as hetrocycle linkers in this project. This class of C-glycosyl amino acids is of interest as new chealtors and as building building blocks for cotranslational glycopeptides synthesis. In the first part, C-Glycosylmethyl pyridylalanines were synthesized 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 α- and β-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. In the second part, tetrazole moiety was constructed via Huisgen 1,3-dipolar cycloaddition between nitriles and organic azides. 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 twostep 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

    Item Type:Thesis (PhD Thesis)
    Date:13 March 2009
    Tutor:Dondoni, Alessandro
    Coordinator:Gilli, Gastone
    Institution:Università degli studi di Ferrara
    PhD:XXI Anno 2006 > SCIENZE CHIMICHE
    Subjects:Area 03 - Scienze chimiche > CHIM/06 Chimica organica
    Uncontrolled Keywords:C-glicosil amminoacidi, C-glicosilmetil piridil alanine, diidropiridine, sintesi di glicopeptidi, sequestranti supportati su polimero, reazione multicomponente di Hantzsch, gruppo funzionale ortogonale, click chemistry, cicloaddizione 1,3-dipolare di Huisgen, 5-sulfonil tetrazoli-1-sostituiti, C-ribosil-O-tetrazolil serine, C-galattosil-Otertazolil serine.
    Deposited on:05 Jul 2009 16:47

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