RESUMO
Reported herein is a new HPLC-based automated synthesizer (HPLC-A) capable of a temperature-controlled synthesis and purification of carbohydrates. The developed platform allows to perform various protecting group manipulations as well as the synthesis of O- and N-glycosides. A fully automated synthesis and purification was showcased in application to different carbohydrate derivatives including glycosides, oligosaccharides, glycopeptides, glycolipids, and nucleosides.
Assuntos
Carboidratos , Oligossacarídeos , Cromatografia Líquida de Alta Pressão , Carboidratos/química , Oligossacarídeos/síntese química , Oligossacarídeos/química , Glicosídeos/química , Glicosídeos/síntese química , Glicolipídeos/química , Glicolipídeos/síntese química , Glicolipídeos/isolamento & purificação , Glicopeptídeos/química , Glicopeptídeos/síntese química , Nucleosídeos/química , Nucleosídeos/síntese química , Automação , TemperaturaRESUMO
The classical Koenigs-Knorr glycosidation of bromides or chlorides promoted with Ag2O or Ag2CO3 works only with reactive substrates (ideally both donor and acceptor). This reaction was found to be practically ineffective with unreactive donors such as per-O-benzoylated mannosyl bromide. Recently, it was discovered that the addition of catalytic (Lewis) acids to a silver salt-promoted reaction has a dramatic effect on the reaction rate and yield. A tentative mechanism for this cooperatively-catalyzed glycosylation reaction has been proposed, and the improved understanding of the reaction led to more efficient protocols and broader applications to a variety of glycosidic linkages. Since Ag2O-mediated activation was introduced by German chemists Koenigs and Knorr, and "cooperatively catalyzed" is Kooperativ Katalysiert in German, we refer to this new reaction as "the 4K reaction."
Assuntos
Glicosídeos , Ácidos de Lewis , Glicosilação , Catálise , BrometosRESUMO
As a part of a general research goal into evaluating the effect of O-protecting groups in sialylation reactions, we compared the reactivities of phenylthio α- and ß-sialyl donors protected at C-4 with tert-butyldimethyl silyl (TBDMS) and tri-isopropylsilyl (TIPS) groups in the coupling with primary and secondary galactosyl acceptors. The effect of the solvent and the donor's anomeric configuration were investigated and compared to previously published data. It is demonstrated that silicon groups at C-4 have a significant influence on sialylation reactions, and in general their overall performance is optimized with the use of acetonitrile.
Assuntos
Silício , Estereoisomerismo , Glicosilação , SolventesRESUMO
A novel 8-O-picoloylated sialyl donor has been developed, and the performance of various picoloylated sialyl donors in glycosylations with primary glycosyl acceptors has been evaluated. 8-O-Picoloyl and 4,9-di-O-picoloyl sialyl donors produced moderate to excellent yields of disaccharides with complete α-stereoselectivities. Synergistic effects between picoloyl and the accompanying O-protecting groups (benzoyl vs acetyl) were evaluated, as well as the effects of triflic acid concentration on the 8-O-picoloyl donor. 1H NMR analysis was also carried out to assess differences in the hydrogen-bonding net between sialyl donors.
Assuntos
Dissacarídeos/síntese química , Ácidos Siálicos/química , Configuração de Carboidratos , Dissacarídeos/química , Glicosilação , Ligação de Hidrogênio , EstereoisomerismoRESUMO
Investigations of methodologies aimed on improving the stereoselective synthesis of sialosides and the efficient assembly of sialic acid glycoconjugates has been the mission of dedicated research groups from the late 1960s. This review presents major accomplishments in the field, with the emphasis on significant breakthroughs and influential synthetic strategies of the last decade.
Assuntos
Glicosídeos/síntese química , Ácido N-Acetilneuramínico/química , Configuração de Carboidratos , Glicosídeos/químicaRESUMO
The stereoselective synthesis of sialic acid glycoconjugates is still a challenge in the field. Surprisingly, little is known on the regioselective O-substitution of sialic acids. Consequently, the effect of O-protecting groups and/or regioselectively protected building blocks in sialylations, remains practically unexplored. O-Picoloyl protecting groups have emerged as novel substituents that have a profound effect on sialylations. Recently, high stereoselectivities were obtained by introducing picoloyl groups at the C-4 and C-7/C-8 positions. However, to understand the relationship between the position of the picoloyl group and its exact effect in sialylations, a convenient access to a wider range of regioselectively picoloylated building blocks is needed. Reported herein is a new method that provides an accessible route to a wide array of regioselectively acylated building blocks. The regioselective introduction of picoloyl groups at various O-positions was achieved either by controlled direct picoloylation or by applying a modified ReSET methodology.
RESUMO
The stereoselective synthesis of sialosides is still one of the major challenges in carbohydrate chemistry. The synthesis and glycosidation of novel sialyl donors bearing a picoloyl substituent at C-4 are reported. High stereoselectivities and faster reactions were observed in the presence of an excess of triflic acid. The acid excess does not have the same effect on conventional sialyl donors, which suggests a possible synergistic effect of the picoloyl substituent and the triflic acid.
RESUMO
The synthesis of C-3-labeled phenylthio sialic acid derivatives and an investigation of stereoselectivity in elimination reactions for the synthesis of 2,3-dehydro derivatives (glycals) is described. The experimental results are consistent with the existence of a conformational change and may be indicative of the intermediacy of an all-axial oxacarbenium ion.
Assuntos
Ácidos Siálicos/síntese química , Compostos de Enxofre/síntese química , Estrutura Molecular , Ácidos Siálicos/química , Estereoisomerismo , Compostos de Enxofre/químicaRESUMO
The profound effect of substituents at C-5 of glycosyl sialosides on their stereoselectivity is well-known although the exact nature of this effect is somewhat less understood. Presented herein is a comparative study of a range of novel sialyl donors with various O-substituents. It is demonstrated that O-substituents at C-4 and C-7 may also have a significant effect on the reactivity of sialyl donors and on the stereoselectivity of chemical sialylation.
Assuntos
Ácidos Siálicos/química , Glicosilação , Estrutura Molecular , EstereoisomerismoRESUMO
Glycoconjugates containing sialic acid are involved in a large variety of biological phenomena, including cell-cell adhesion, recognition by viruses and bacteria, and oncogenesis. Therefore, they are important synthetic targets for the design of drugs and vaccines. In the last decades, different methodologies that improve yield and stereoselectivity in sialylation reactions have been investigated. This review summarizes the latest developments in the synthesis of C-5 modified sialic acid glycosyl donors and glycosyl acceptors and their application in the synthesis of alpha-sialosides.
Assuntos
Ácido N-Acetilneuramínico/análogos & derivados , Ácido N-Acetilneuramínico/química , Azidas/química , Oxazolidinonas/química , Ácido Trifluoracético/químicaRESUMO
As a part of a program for developing new versatile building blocks for stereoselective glycosylation and convergent oligosaccharide synthesis, we demonstrated that S-benzoxazolyl (SBox) glycosides are stable toward major protecting group manipulations employed in carbohydrate chemistry. On the other hand, they can be glycosidated under relatively mild reaction conditions to afford either 1,2-trans or 1,2-cis-linked disaccharides. Selective and chemoselective activations of the SBox moiety were also proved to be feasible, which was demonstrated by synthesizing a number of oligosaccharide sequences.
Assuntos
Compostos Azo/química , Benzeno/química , Oligossacarídeos/síntese química , Glicosídeos/química , Estrutura Molecular , Oligossacarídeos/químicaRESUMO
[reaction: see text] Novel glycosyl donors, S-benzoxazolyl (SBox) glycosides, have been synthesized, tested toward various protecting group manipulations, and applied to the highly stereoselective 1,2-cis glycosylation. These compounds fulfill the requirements for a modern glycosyl donor such as accessibility, high stability toward protecting group manipulations, and mild activation conditions. It was also demonstrated that SBox glycosides withstand other glycosyl donor activation conditions and therefore allow selective glycosylations of O-pentenyl and thioglycosides.