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.
Fluorescent carbon dots (FCDs) are an emerging class of nanomaterials made from carbon sources that have been hailed as potential non-toxic replacements to traditional semiconductor quantum dots ...(QDs). Particularly in the areas of live imaging and drug delivery, due to their water solubility, low toxicity and photo- and chemical stability. Carbohydrates are readily available chiral biomolecules in nature which offer an attractive and cheap starting material from which to synthesise FCDs with distinct features and interesting applications. This mini-review article will cover the progress in the development of FCDs prepared from carbohydrate sources with an emphasis on their synthesis, functionalization and technical applications, including discussions on current challenges.
Multivalent carbohydrate-mediated interactions are key to many biological processes including disease mechanisms. In order to study these important glycan-mediated interactions at a molecular level, ...carbon nanoforms such as fullerenes, carbon nanotubes or graphene and their derivatives have been identified as promising biocompatible scaffolds that can mimic the multivalent presentation of biologically relevant glycans. In this mini-review, we will summarize the most relevant examples of the last few years in the context of their applications.
Carbohydrates play a pivotal role in biological systems and present an opportunity to develop potent carbohydrate‐derived therapeutics and diagnostic tools for the treatment and detection of disease. ...To better comprehend the biological functions of carbohydrates, access to pure and structurally defined oligosaccharides is needed. Oligosaccharides are commonly synthesized by chemical means; however, despite progress in glycosylation chemistry, the efficient and stereoselective formation of glycosidic bonds by mild, nontoxic and low‐cost methods remains a challenge. Organocatalysis is an exciting field that utilizes small organic molecules to effect chemical transformation where traditionally transition metal catalysis would be required. This microreview presents recent advances in the application of organocatalysis to carbohydrate chemistry and in particular to the stereoselective synthesis of oligosaccharides.
Despite progress in the synthesis of oligosaccharides, the efficient and stereoselective formation of glycosidic bonds by mild, nontoxic, and low‐cost methods remains a challenge. This microreview presents recent advances in the application of organocatalysis to carbohydrate chemistry and in particular to the stereoselective synthesis of oligosaccharides.
Au(I) in combination with AgOTf enables the unprecedented direct and α-stereoselective catalytic synthesis of deoxyglycosides from glycals. Mechanistic investigations suggest that the reaction ...proceeds via Au(I)-catalyzed hydrofunctionalization of the enol ether glycoside. The room temperature reaction is high yielding and amenable to a wide range of glycal donors and OH nucleophiles.
Pd(MeCN)2Cl2 enables the α-stereoselective catalytic synthesis of 2,3-unsaturated O-glycosides from O(3)-acylated glycals without the requirement for additives to preactivate either donor or ...nucleophile. Mechanistic studies suggest that, unlike traditional (η3-allyl)palladium-mediated processes, the reaction proceeds via an alkoxy-palladium intermediate that increases the proton acidity and oxygen nucleophilicity of the alcohol. The method is exemplified with the synthesis of a range of glycosides and glycoconjugates of synthetic utility.
Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with ...anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy.
Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses.
In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P = .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005), and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02).
The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.
Antimicrobial resistance is a recognized global challenge. Tools for bacterial detection can combat antimicrobial resistance by facilitating evidence-based antibiotic prescribing, thus avoiding their ...overprescription, which contributes to the spread of resistance. Unfortunately, traditional culture-based identification methods take at least a day, while emerging alternatives are limited by high cost and a requirement for skilled operators. Moreover, photodynamic inactivation of bacteria promoted by photosensitisers could be considered as one of the most promising strategies in the fight against multidrug resistance pathogens. In this context, carbon dots (CDs) have been identified as a promising class of photosensitiser nanomaterials for the specific detection and inactivation of different bacterial species. CDs possess exceptional and tuneable chemical and photoelectric properties that make them excellent candidates for antibacterial theranostic applications, such as great chemical stability, high water solubility, low toxicity and excellent biocompatibility. In this review, we will summarize the most recent advances on the use of CDs as antimicrobial agents, including the most commonly used methodologies for CD and CD/composites syntheses and their antibacterial properties in both in vitro and in vivo models developed in the last 3 years.
The stereoselective synthesis of oligosaccharides remains one of the biggest challenges in carbohydrate chemistry. Many factors, including reaction conditions and the type of glycosyl donor and ...acceptor used, can affect the outcome of glycosylation reactions. In this Perspective, we discuss methods aimed to control the reactivity and stereoselectivity of glycosylation reactions using conformationally constrained glycosyl donors, with a focus on more recently developed chemistry.
G‐quadruplexes (G4) are four‐stranded structures formed from guanine‐rich oligonucleotides. Their defined 3D structures and polymorphic nature set them apart from classical nucleic acid morphology ...and suggest a range of potential applications in the development of functional materials. Meanwhile, the occurrence of G4 across the genomes of animals, plants and pathogens suggests roles for these structures in biology that may be exploited for therapeutic effect. Hundreds of G4 ligands are reported to bind these sequences with high specificity and affinity, but such ligands can also be engineered to do more than simply associate with G4 in a straightforward host‐guest fashion. Ligands have been developed that can switch G4 topology, direct the selective covalent modification of nucleic acid structures, or respond to external stimuli to permit spatiotemporal control of their activity. Herein we survey the main themes of such “value‐added” G4 ligands and consider the opportunities and challenges of their potential applications.
G‐quadruplex (G4) ligands can do much more than simply associate with nucleic acids in a straightforward host‐guest fashion. This review examines what else can be accomplished with G4‐targeting molecules and considers the opportunities and challenges towards the development of potential applications in biology and nanotechnology.
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