RESUMO
Reported herein is the synthesis of a number of building blocks of 2-amino-2-deoxy-d-mannose from common d-glucose precursors.
Assuntos
Glucose/química , Hexosaminas/síntese química , Manose/análogos & derivados , Sequência de Carboidratos , Hexosaminas/química , Manose/químicaRESUMO
Presented herein is a study of the conformation and reactivity of highly reactive thioglycoside donors. The structural studies have been conducted using NMR spectroscopy and computational methods. The reactivity of these donors has been investigated in bromine-promoted glycosylations of aliphatic and sugar alcohols. Swift reaction times, high yields, and respectable 1,2-cis stereoselectivity were observed in a majority of these glycosylations.
RESUMO
In an attempt to refine the H-bond-mediated Aglycone Delivery (HAD) glycosylation reaction reported herein is the synthesis of ß-glucosides using an ethylthio glucoside donor equipped with the remote 6-O-picoloyl substituent. Upon examining various aliphatic, aromatic, and carbohydrate acceptors, it was determined that both electronic and steric factors may greatly affect the stereoselectivity of the HAD reaction with this donor.
Assuntos
Glucosídeos/síntese química , Configuração de Carboidratos , Glucosídeos/química , Glicosilação , Ligação de Hidrogênio , EstereoisomerismoRESUMO
In an attempt to refine a CAN-mediated synthesis of 1,3,4,6-tetra-O-acetyl-α-d-glucopyranose (2-OH glucose) we unexpectedly discovered that this reaction proceeds via the intermediacy of glycosyl nitrates. Improved mechanistic understanding of this reaction led to the development of a more versatile synthesis of 2-OH glucose from a variety of precursors. Also demonstrated is the conversion of 2-OH glucose into a variety of building blocks differentially protected at C-2, a position that is generally hard to protect regioselectively in the glucopyranose series.
Assuntos
Glucose/química , Glucose/síntese química , Nitratos/química , Técnicas de Química Sintética , Glicosilação , Piranos/químicaRESUMO
A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete ß-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.
Assuntos
Glicosídeos/química , Oligossacarídeos/síntese química , Configuração de Carboidratos , Glicosilação , Oligossacarídeos/química , EstereoisomerismoRESUMO
Previously we communicated 3,3-difluoroxindole (HOFox) - mediated glycosylations wherein 3,3-difluoro-3H-indol-2-yl (OFox) imidates were found to be key intermediates. Both the in situ synthesis from the corresponding glycosyl bromides and activation of the OFox imidates could be conducted in a regenerative fashion. Herein, we extend this study with the main focus on the synthesis of various OFox imidates and their investigation as glycosyl donors for chemical 1,2-cis and 1,2-trans glycosylation.
Assuntos
Imidoésteres/química , Indóis/química , Glicosilação , Imidoésteres/síntese química , Indóis/síntese química , Estrutura Molecular , EstereoisomerismoRESUMO
The chemical synthesis of the repeating unit of S. aureus capsular polysaccharide type 5 equipped with capping methyl groups at the points of propagation of the polysaccharide sequence is described. This model compound was designed to study activation of the full length polysaccharide for conjugation to a carrier protein.
Assuntos
Cápsulas Bacterianas/química , Polissacarídeos Bacterianos/química , Polissacarídeos/química , Staphylococcus aureus/química , Azidas/química , Química Orgânica , Metilação , Oxigênio/química , Solventes/química , Trissacarídeos/química , Ácidos Urônicos/químicaRESUMO
2-O-Picolinyl protected glycosyl donors lead to the formation of 1,2-trans glycosides with complete stereoselectivity. This is due to the participatory effect of the picolinyl nitrogen that is able to block the bottom face of the ring via a six-membered cyclic intermediate. Herein we demonstrate that if the nitrogen atom of the O-picolinyl moiety is temporarily blocked by coordination to the metal center (Pd), it becomes unavailable to participate in glycosylation and hence the stereoselectivity of 2-O-picolinyl-assisted glycosylations can be "switched".
Assuntos
Glicosídeos/química , Picolinas/química , Cristalografia por Raios X , Glicosídeos/síntese química , Glicosilação , Modelos Moleculares , EstereoisomerismoRESUMO
Remote 6-O-picolinyl or 6-O-picoloyl substituents often provide high ß-selectivity due to H-bond-mediated aglycone delivery (HAD). Herein it has been demonstrated that if the nitrogen atom of the 6-O-picolinyl or picoloyl moiety is temporarily blocked by coordination to a metal center (Pd), it cannot engage in HAD-mediated ß-glycosylation. Hence, the stereoselectivity of 6-O-picolinyl/picoloyl-assisted glycosylations can be "switched" to α-selectivity.
RESUMO
The first synthesis of the repeating unit of S. aureus capsular polysaccharide type 8 is described. The repeating unit is an unusual trisaccharide sequence of three uncommon sugars, all connected via 1,2-cis linkages. The synthetic trisaccharide was equipped with capping methyl groups at the points of propagation of the polysaccharide sequence.
Assuntos
Polissacarídeos Bacterianos/síntese química , Staphylococcus aureus/química , Configuração de Carboidratos , Sequência de Carboidratos , Polissacarídeos Bacterianos/químicaRESUMO
Described herein is the expansion of the picoloyl protecting-group assisted H-bond mediated aglycone delivery (HAD) method recently introduced by our laboratory. At first it was noticed that high α-stereoselectivity is only obtained with S-ethyl glycosyl donors and only in the presence of dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST), in high dilution, and low temperature. Combining the mechanistic studies of the HAD reaction and bromine-promoted glycosylations allowed a very effective method to be devised that allows for highly stereoselective α-glycosidation of practically all common leaving groups (S-phenyl, S-tolyl, S/O-imidates) at regular concentrations and ambient temperature.
RESUMO
A Hydrogen bond mediated aglycone delivery (HAD) method was applied to the synthesis of α-glucans, which are abundant in nature, but as targets represent a notable challenge to chemists. The synthesis of linear oligosaccharide sequences was accomplished in complete stereoselectivity in all glycosylations. The efficacy of HAD may diminish with the increased bulk of the glycosyl acceptor, and may be an important factor for the syntheses of oligomers beyond pentasaccharides. The synthesis of a branched structure proved more challenging, particularly with bulky trisaccharide acceptors.
Assuntos
Glucanos/química , Cobre/química , Glucanos/síntese química , Glicosilação , Hidrogênio/química , Ligação de Hidrogênio , Mesilatos/química , Oligossacarídeos/química , EstereoisomerismoRESUMO
O-Picoloyl groups at remote positions can mediate the course of glycosylation reactions by providing high facial selectivity for the H-bond-mediated attack of the glycosyl acceptor. A new practical method for the stereoselective synthesis of ß-mannosides at ambient temperature is presented.
Assuntos
Hidrogênio/química , Manosídeos/química , Glicosilação , Ligação de Hidrogênio , Estrutura Molecular , EstereoisomerismoRESUMO
O-picolinyl and O-picoloyl groups at remote positions (C-3, C-4, and C-6) can mediate glycosylation reactions by providing high or even complete facial selectivity for the attack of the glycosyl acceptor. The set of data presented herein offers a strong evidence of the intermolecular H-bond tethering between the glycosyl donor and glycosyl acceptor counterparts while providing a practical new methodology for the synthesis of either 1,2-cis or 1,2-trans linkages. Challenging glycosidic linkages including α-gluco, ß-manno, and ß-rhamno have seen obtained with high or complete stereocontrol.
RESUMO
Elaborating on previous studies by Lemieux for highly reactive "armed" bromides, we discovered that ß-bromide of the superdisarmed (2-O-benzyl-3,4,6-tri-O-benzoyl) series can be directly obtained from the thioglycoside precursor. When this bromide is glycosidated, α-glycosides form exclusively; however, the yields of such transformations may be low due to the competing anomerization into α-bromide that is totally unreactive under the established reaction conditions.