Thiocarbonyl as a Switchable Relay-Auxiliary Group in Carbohydrate Synthesis.
TL;DR: In this paper, a multifunctional O-phenyl thiocarbonyl (O(C═S)OPh) group was introduced in glycosylation reactions.
About: This article is published in Organic Letters.The article was published on 2021-07-16. It has received 6 citations till now. The article focuses on the topics: Glycosylation & Carbohydrate synthesis.
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10 Mar 2022
TL;DR: It is reported that N-phenyltrifluoroacetimidoyl (PTFAI), a well-known leaving group for catalytic glycosylation, can act as a stereodirecting group for the challenging 1,2-cis α-glycosylating of trisaccharide heparins.
Abstract: The anomeric configuration can greatly affect the biological functions and activities of carbohydrates. Herein, we report that N-phenyltrifluoroacetimidoyl (PTFAI), a well-known leaving group for catalytic glycosylation, can act as a stereodirecting group for the challenging 1,2-cis α-glycosylation. Utilizing rapidly accessible 1,6-di-OPTFAI glycosyl donors, TMSOTf-catalyzed glycosylation occurred with excellent α-selectivity and broad substrate scope, and the remaining 6-OPTFAI group can be cleaved chemoselectively. The remote participation of 6-OPTFAI is supported by the first characterization of the crucial 1,6-bridged bicyclic oxazepinium ion intermediates by low-temperature NMR spectroscopy. These cations were found to be relatively stable and mainly responsible for the present stereoselectivities. Further application is highlighted in glycosylation reactions toward trisaccharide heparins as well as the convergent synthesis of chacotriose derivatives using a bulky 2,4-di-O-glycosylated donor.
8 citations
TL;DR: In this article , the electron density in acyl protecting groups influences the stereoselectivity by fine-tuning the efficiency of remote participation, and an α-selective galactose building block for glycosynthesis is developed based on rational considerations and is subsequently employed in automated glycan assembly.
Abstract: The stereoselective formation of 1,2-cis-glycosidic bonds is a major bottleneck in the synthesis of carbohydrates. We here investigate how the electron density in acyl protecting groups influences the stereoselectivity by fine-tuning the efficiency of remote participation. Electron-rich C4-pivaloylated galactose building blocks show an unprecedented α-selectivity. The trifluoroacetylated counterpart with electron-withdrawing groups, on the other hand, exhibits a lower selectivity. Cryogenic infrared spectroscopy in helium nanodroplets and density functional theory calculations revealed the existence of dioxolenium-type intermediates for this reaction, which suggests that remote participation of the pivaloyl protecting group is the origin of the high α-selectivity of the pivaloylated building blocks. According to these findings, an α-selective galactose building block for glycosynthesis is developed based on rational considerations and is subsequently employed in automated glycan assembly exhibiting complete stereoselectivity. Based on the obtained selectivities in the glycosylation reactions and the results from infrared spectroscopy and density functional theory, we suggest a mechanism by which these reactions could proceed.
3 citations
TL;DR: A wide range of protected and unprotected 1-thiosugars derived from glucose, glucosamine, galactose, mannose, ribose, maltose, and lactose underwent cross-coupling reactions with functionalized aryldiazonium salts in the presence of copper(I) chloride and DBU.
Abstract: Preparation of S-aryl thioglycosides from 1-thiosugars via S-arylation was demonstrated under mild reaction conditions. A wide range of protected and unprotected 1-thiosugars derived from glucose, glucosamine, galactose, mannose, ribose, maltose, and lactose underwent cross-coupling reactions with functionalized aryldiazonium salts in the presence of copper(I) chloride and DBU. The desired products were obtained in 55-88% yields within 5 min. Various functional groups, including halogens, were tolerated under standard reaction conditions. Synthesis of the biologically relevant antidiabetic dapagliflozin S-analogue and arbutin S-analogues (tyrosinase inhibitors) was demonstrated.
2 citations
TL;DR: In this article , the authors describe the technological solutions that have advanced glycochemistry using automated glycan assembly, flow chemistry and data science as examples and highlight how the synergies between these different technologies can further advance the field, with progress toward the realization of a self-driving lab for glycan synthesis.
Abstract: The synthesis of defined oligosaccharides is a complex task. Several enabling technologies have been introduced in the last two decades to facilitate synthetic access to these valuable biomolecules. In this concept, we describe the technological solutions that have advanced glycochemistry using automated glycan assembly, flow chemistry and data science as examples. We highlight how the synergies between these different technologies can further advance the field, with progress toward the realization of a self‐driving lab for glycan synthesis.
1 citations
TL;DR: In this paper , N-phenyltrifluoroacetimidoyl (PTFAI) was used as a stereodirecting group for 1,2-cis α-glycosylation.
Abstract: The anomeric configuration can greatly affect the biological functions and activities of carbohydrates. Herein, we report that N-phenyltrifluoroacetimidoyl (PTFAI), a well-known leaving group for catalytic glycosylation, can act as a stereodirecting group for the challenging 1,2-cis α-glycosylation. Utilizing rapidly accessible 1,6-di-OPTFAI glycosyl donors, TMSOTf-catalyzed glycosylation occurred with excellent α-selectivity and broad substrate scope, and the remaining 6-OPTFAI group can be cleaved chemoselectively. The remote participation of 6-OPTFAI is supported by the first characterization of the crucial 1,6-bridged bicyclic oxazepinium ion intermediates by low-temperature NMR spectroscopy. These cations were found to be relatively stable and mainly responsible for the present stereoselectivities. Further application is highlighted in glycosylation reactions toward trisaccharide heparins as well as the convergent synthesis of chacotriose derivatives using a bulky 2,4-di-O-glycosylated donor.
1 citations
References
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TL;DR: Synthetic oligosaccharides and glycoconjugates are increasingly used as probes for biological research and as lead compounds for drug and vaccine discovery, and the power of carbohydrate chemistry is highlighted by an ability to synthesize glycoproteins.
Abstract: Synthetic oligosaccharides and glycoconjugates are increasingly used as probes for biological research and as lead compounds for drug and vaccine discovery. These endeavors are, however, complicated by a lack of general methods for the routine preparation of this important class of compounds. Recent development such as one-pot multi-step protecting group manipulations, the use of unified monosaccharide building blocks, the introduction of stereoselective glycosylation protocols, and convergent strategies for oligosaccharide assembly, are beginning to address these problems. Furthermore, oligosaccharide synthesis can be facilitated by chemo-enzymatic methods, which employ a range of glycosyl transferases to modify a synthetic oligosaccharide precursor. Glycosynthases, which are mutant glycosidases, that can readily form glycosidic linkages are addressing a lack of a wide range glycosyltransferases. The power of carbohydrate chemistry is highlighted by an ability to synthesize glycoproteins.
488 citations
TL;DR: The current understanding of O-GlcNAcylation in cancer and its emerging functions in transcriptional regulation at the level of chromatin and transcription factors are summarized.
Abstract: O-GlcNAcylation is the covalent attachment of β-D-N-acetylglucosamine (GlcNAc) sugars to serine or threonine residues of nuclear and cytoplasmic proteins, and it is involved in extensive crosstalk with other post-translational modifications, such as phosphorylation. O-GlcNAcylation is becoming increasing realized as having important roles in cancer-relevant processes, such as cell signalling, transcription, cell division, metabolism and cytoskeletal regulation. However, currently little is known about the specific roles of aberrant O-GlcNAcylation in cancer. In this Opinion article, we summarize the current understanding of O-GlcNAcylation in cancer and its emerging functions in transcriptional regulation at the level of chromatin and transcription factors.
386 citations
TL;DR: Recent advances in the development of fully synthetic sub-unit carbohydrate-based cancer vaccines will be discussed.
201 citations
TL;DR: This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter.
Abstract: Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.
194 citations
TL;DR: This review describes the methodologies for one- Pot protection and their one-pot glycosylation into the complex glycans and the chronological developments associated with automated syntheses of oligosaccharides.
Abstract: Carbohydrates, which are ubiquitously distributed throughout the three domains of life, play significant roles in a variety of vital biological processes. Access to unique and homogeneous carbohydrate materials is important to understand their physical properties, biological functions, and disease-related features. It is difficult to isolate carbohydrates in acceptable purity and amounts from natural sources. Therefore, complex saccharides with well-defined structures are often most conviently accessed through chemical syntheses. Two major hurdles, regioselective protection and stereoselective glycosylation, are faced by carbohydrate chemists in synthesizing these highly complicated molecules. Over the past few years, there has been a radical change in tackling these problems and speeding up the synthesis of oligosaccharides. This is largely due to the development of one–pot protection, one–pot glycosylation, and one–pot protection–glycosylation protocols and streamlined approaches to orthogonally protect...
175 citations