alpha-Glycosyl amides represent a little known class of non-hydrolysable monosaccharide derivatives that may find useful application as sugar mimics and neo-glycoconjugates. Their stereoselective synthesis has proven difficult because glycosyl amines are not configurationally stable and undergo easy alpha to betaanomerization. Various methods have been proposed to get around this problem by reducing alpha glycosyl azides in the presence of acylating agents, but only a few have been reported to afford alpha-glycosyl amides, most of which require two steps and/or have been described for a limited number of substrates. Much work has been devoted to the Staudinger reduction/acylation process, which consists in the reduction of glycosyl azides with phosphines in the presence of carboxylic acids or derivatives. In this PhD thesis we have developed a stereoconservative Staudinger ligation of unprotected fluorophenyl esters to afford α- and β-N-glycosyl amino acids. The ligation method works reliably well for unprotected β-azides of the gluco, galacto and fuco series. Lower yields (ca. 50%) were obtained with a β-glucosyl-Nacetyl azide. The reaction of an α-glucosyl azide also led to major improvements compared with the use of non-fluorinated phosphines. All the N-glycosyl amino acid products can be isolated and by-products removed from the crude reaction mixtures by simple water extraction. alpha- or beta-glycofuranosyl amides can be synthesized with high stereoselectivity by traceless Staudinger ligation using a non-fluorinated phosphines, starting from unprotected beta-glycofuranosyl azide or tetra-O-acetyl-beta-glycofuranosyl azide, respectively. In particular, the resulting galactofuranosyl amides are hitherto unknown molecules, with interesting potential as inhibitors of mycobacterial growth especially for the alpha compounds.

STEREOSELECTIVE SYNTHESIS OF GLYCOSYL AMIDES BY TRACELESS STAUDINGER LIGATION OF GLYCOSYL AZIDES / F. Nisic ; tutor: Anna Bernardi ; coordinator: Silvia Ardizzoni. DIPARTIMENTO DI CHIMICA INORGANICA, METALLORGANICA E ANALITICA "Lamberto Malatesta", 2010 Dec 09. 23. ciclo, Anno Accademico 2009/2010. [10.13130/nisic-filippo_phd2010-12-09].

STEREOSELECTIVE SYNTHESIS OF GLYCOSYL AMIDES BY TRACELESS STAUDINGER LIGATION OF GLYCOSYL AZIDES

F. Nisic
2010

Abstract

alpha-Glycosyl amides represent a little known class of non-hydrolysable monosaccharide derivatives that may find useful application as sugar mimics and neo-glycoconjugates. Their stereoselective synthesis has proven difficult because glycosyl amines are not configurationally stable and undergo easy alpha to betaanomerization. Various methods have been proposed to get around this problem by reducing alpha glycosyl azides in the presence of acylating agents, but only a few have been reported to afford alpha-glycosyl amides, most of which require two steps and/or have been described for a limited number of substrates. Much work has been devoted to the Staudinger reduction/acylation process, which consists in the reduction of glycosyl azides with phosphines in the presence of carboxylic acids or derivatives. In this PhD thesis we have developed a stereoconservative Staudinger ligation of unprotected fluorophenyl esters to afford α- and β-N-glycosyl amino acids. The ligation method works reliably well for unprotected β-azides of the gluco, galacto and fuco series. Lower yields (ca. 50%) were obtained with a β-glucosyl-Nacetyl azide. The reaction of an α-glucosyl azide also led to major improvements compared with the use of non-fluorinated phosphines. All the N-glycosyl amino acid products can be isolated and by-products removed from the crude reaction mixtures by simple water extraction. alpha- or beta-glycofuranosyl amides can be synthesized with high stereoselectivity by traceless Staudinger ligation using a non-fluorinated phosphines, starting from unprotected beta-glycofuranosyl azide or tetra-O-acetyl-beta-glycofuranosyl azide, respectively. In particular, the resulting galactofuranosyl amides are hitherto unknown molecules, with interesting potential as inhibitors of mycobacterial growth especially for the alpha compounds.
9-dic-2010
Settore CHIM/06 - Chimica Organica
glycoconjugates ; glycosyl amides ; glycopeptides ;
BERNARDI, ANNA
ARDIZZONE, SILVIA
Doctoral Thesis
STEREOSELECTIVE SYNTHESIS OF GLYCOSYL AMIDES BY TRACELESS STAUDINGER LIGATION OF GLYCOSYL AZIDES / F. Nisic ; tutor: Anna Bernardi ; coordinator: Silvia Ardizzoni. DIPARTIMENTO DI CHIMICA INORGANICA, METALLORGANICA E ANALITICA "Lamberto Malatesta", 2010 Dec 09. 23. ciclo, Anno Accademico 2009/2010. [10.13130/nisic-filippo_phd2010-12-09].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/150139
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