Mechanistic studies of rearrangements during the ring expansions of cyclopropanated carbohydrates

Deuterium-labeling studies have been performed on the ring expansion of cyclopropanated carbohydrates. From these studies, mechanisms have been proposed for two unusual rearrangements. In addition, a selective deprotection of the 1,3-di-tert-butylsilyl ether protecting group at the secondary position versus the primary position has been observed. This is a high yielding transformation with the potential for general synthetic utility.     

Potentiometric determination of d(+)glucose, d(+)mannose or d(-)fructose in a mixture of hexoses and pentoses, by using streptococcus mutans fermentation

A potentiometric sensor has been developed, based on selective fermentation of carbohydrates by Streptococcus mutans. This combination of bacterial action and a glass electrode responds to beta-d(+)glucose, d(+)mannose and beta-d(-)fructose over a narrow concentration range, with a response time of 4 min, and has negligible response to other hexoses and pentoses.     

Site‐Selective O‐Arylation of Glycosides

Direct and site‐selective O‐arylation of carbohydrates has been a challenge in synthesis. Herein we report a method based on copper‐catalyzed O‐arylation to address this challenge. Proper choice of the ancillary ligand on copper is critical for the efficiency and site selectivity of this transformation. This method features mild conditions, tolerates various functional groups, and demonstrates broad substrate scope.     

Lignin: its functions and successive flow

Phenolic lignin-based polymers with structure-variable function have originally been designed, and a process has been developed for synthesizing them directly from native lignins. The key point of the process is to set up two different solvents, which are immiscible each other, for selective modification and separation of lignin and carbohydrates: hydrophobic solvent for hydrophobic lignin and hydrophilic solvent for hydrophilic carbohydrates. The native lignins, three dimensional network polymers, are subjected to selective modifications at the interface between both phases to give linear type polymers (lignophenols) composed mainly of 1,1-bis(aryl)propane type units, almost quantitatively. The process provides a new system for successively utilizing lignocellulosics in the molecular level.     

Conformational Studies of Oligosaccharides

The conformation of a molecule strongly affects its function, as demonstrated for peptides and nucleic acids. This correlation is much less established for carbohydrates, the most abundant organic materials in nature. Recent advances in synthetic and analytical techniques have enabled the study of carbohydrates at the molecular level. Recurrent structural features were identified as responsible for particular biological activities or material properties. In this Minireview, recent achievements in the structural characterization of carbohydrates, enabled by systematic studies of chemically defined oligosaccharides, are discussed. These findings can guide the development of more potent glycomimetics. Synthetic carbohydrate materials by design can be envisioned.     

Carbohydrates as the next frontier in pharmaceutical research

Synthetic carbohydrates and glycoconjugates are used to study their roles in biological important processes such as inflammation, cell-cell recognition, immunological response, metastasis, and fertilization. The development of an automated oligosaccharide synthesizer greatly accelerates the assembly of complex, naturally occurring carbohydrates as well as chemically modified oligosaccharide structures and promises to have major impact on the field of glycobiology. Tools such as microarrays, surface plasmon resonance spectroscopy, and fluorescent carbohydrate conjugates to map interactions of carbohydrates in biological systems are presented. Case studies of the successful application of carbohydrates as active agents are discussed, for example, fully synthetic oligosaccharide vaccines to combat tropical diseases (e.g., malaria), bacterial infections (e.g., tuberculosis), viral infections such as HIV, and cancer. Aminoglycosides serve as examples of drugs acting through carbohydrate-nucleic-acid interactions, while heparin works by carbohydrate-protein interactions. A general, modular strategy for the complete stereoselective synthesis of defined heparin oligosaccharides is presented. A carbohydrate-functionalized fluorescent polymer has been shown to detect miniscule amounts of bacteria faster than commonly used methods.     

Carbohydrate chemistry in drug discovery

The multitude of roles that carbohydrates and their glyco-conjugates play in biological processes has stimulated great interest in determining the nature of their interactions in both normal and diseased states. Manipulating such interactions will provide leads for drug discovery. Of the major classes of biomolecule, carbohydrates are the most structurally diverse. This hetereogeneity makes isolation of pure samples, and in sufficient amounts, from biological sources extremely difficult. Chemical synthesis offers the advantage of producing pure and structurally defined oligosaccharides for biological investigations. Although the complex nature of carbohydrates means that this is challenging, recent advances in the field have facilitated access to these molecules. The synthesis and isolation of oligosaccharides combined with progress in glycoarray technology have aided the identification of new carbohydrate-binding drug targets. This review aims to provide an overview of the latest advancements in carbohydrate chemistry and the role of these complex molecules in drug discovery, focusing particularly on synthetic methodologies, glycosaminoglycans, glycoprotein synthesis and vaccine development over the last few years.     

利用硅基迁移反应简便合成选择性苄基保护的糖类衍生物

羟基保护是糖化学合成的重要组成部分,羟基选择性部分保护的糖类衍生物中间体的合成往往需要多步反应或使用特殊试剂。本文以不同的甲基O-叔丁基二甲硅基糖苷为起始物,探讨了利用碱性条件下的硅基迁移反应合成选择性保护的糖类衍生物中间体的方法。例如,甲基6-O-叔丁基二甲硅基a-D-吡喃葡萄糖苷在NaH及BnBr 作用下进行苄基化反应,随后在酸性条件下脱去硅基,主要得到6-O→4-O硅基迁移的产物,甲基2,3,6-三-O-苄基a-D-吡喃葡萄糖苷。提出了一种简便合成选择性苄基保护的甲基2,3,6-三-O-苄基a-D-吡喃葡萄糖苷的有效方法。     

Carbohydrate arrays for functional studies of carbohydrates

Carbohydrates, as components of glycoproteins, glycolipids and proteoglycans, play an important biological role as recognition markers through carbohydrate-protein interactions. For the most part, biophysical and biochemical methods have been used to analyze these biomolecular interactions. In contrast, less attention has been given to the development of high-throughput procedures to elucidate carbohydrate-protein recognition events. Recently, carbohydrate arrays were developed and employed as a novel high-throughput analytic tool for monitoring carbohydrate-protein interactions. This technique has been used to profile protein binding and enzymatic activity. The results have shown that carbohydrate binding to the corresponding lectins is highly selective and that the relative binding affinities are well correlated with those obtained from solution-based assays. In addition, this effort demonstrated that carbohydrate arrays could be also utilized to identify and characterize novel carbohydrate-binding proteins or carbohydrate-processing enzymes. Finally, the results of this investigation showed that lectin-carbohydrate binding affinities could be quantitatively assessed by determining IC50 values for soluble carbohydrates with the carbohydrate arrays. The results of these studies suggest that carbohydrate arrays have the potential of playing an important role in basic researches, the diagnoses of diseases and drug discovery.     

Carbohydrate-based fluorometric and colorimetric sensors for Cu2+ ion recognition

The development of optical sensors using carbohydrates for selective detection of copper in water and living system has been an active research area in the past few years because of widespread applications and biological importance of copper. Introduction of carbohydrate to design the sensors is an attractive field of research because of its chiral entities with hydroxyl groups and oxygen atoms, controlled ring-flipping capability, abundance, and biocompatibility. This minireview focuses on the reported carbohydrate-based fluorescent and colorimetric sensors for Cu²⁺ detection and is organized according to their structural categories such as triazole-linked, imine-linked, and non–triazole-/imine-linked carbohydrate–based sensors. To the best of our knowledge, this is the first review article focused on carbohydrate-based Cu²⁺ sensors.     

β‐Selective C‐Glycosylation and its Application in the Synthesis of Scleropentaside A

C‐Glycosides are carbohydrates that bear a C?C bond to an aglycon at the anomeric center. Due to their high stability towards chemical and enzymatic hydrolysis, these compounds are widely used as carbohydrate mimics in drug development. Herein, we report a general and exclusively β‐selective method for the synthesis of a naturally abundant acyl‐C‐glycosidic structural motif first found in the scleropentaside natural product family. A Corey–Seebach umpolung reaction as the key step in the synthesis of scleropentaside A and analogues enables the β‐selective construction of the anomeric C?C bond starting from unprotected carbohydrates in only four steps. The one‐pot approach is highly atom‐efficient and avoids the use of toxic heavy metals.     

Protection Strategies Enable Selective Conversion of Biomass

Selective and economic conversion of lignocellulosic biomass components to bio‐based fuels and chemicals is the major goal of biorefineries, but low yields and selectivity for fuel precursors such as sugars, furanics, and lignin‐derived monomers pose significant disadvantages in process economics. In this Minireview we summarize the existing protection strategies used in biomass chemocatalytic conversion processes and focus the discussions on the mechanisms, challenges, and opportunities of each strategy. We introduce a concept of using analogous methods to manipulate biomass catalytic conversion pathways during the upgrading of carbohydrates to fuels and chemicals. This Minireview may provide new insights into the development of selective biorefining processes from a different perspective, expanding the options for selective conversion of biomass to fuels and chemicals.     

Total determination of metal-binding carbohydrates in plant extracts by using FIA with electrochemical detection

FIA with pulsed amperometric detection (PAD) is used for the determination of metal-binding carbohydrates in plant extracts. Results of direct FIA measurements agree very well with those of corresponding HPLC-PAD analyses. The proposed method is used to determine total carbohydrates in isolated low-molecular-weight fractions of plant roots, which have been obtained after extraction at different pH values. The results are compared with those obtained by corresponding metal determinations (Ca, Mg, Zn, Mn) by AAS and also with constant potential amperometric detection at a copper working electrode. The latter detection mode is more sensitive, but less selective for carbohydrates.     

Zirconium(IV) chloride catalyzed new and efficient protocol for the selective cleavage of p-methoxybenzyl ethers

A highly selective and efficient method for the unmasking of p-methoxybenzyl (PMB) ethers and esters has been developed by use of 20 mol % of zirconium(IV) chloride as Lewis acid in acetonitrile. The present method is very fast, and the conditions are tolerable to a variety of acid/base-sensitive protecting groups and substrates such as carbohydrates, terpenes, and amino acids. The products are obtained in good to high yields.     

The versatility of carbohydrates in antimicrobial applications

The worsening situation of global drug resistance is urgently demanding for novel antimicrobial agents. Considerable efforts have been concentrated on developing new antibacterial therapies with new mode of actions, exerting no selective pressure on bacterial mutation, and minimizing toxicity to host cells. In this context, active targeting can greatly contribute to selectivity between pathogens and mammalian cells in which carbohydrates, playing important roles in numerous biological processes, can be employed as targeting ligands or “trojan horse.” This short account has discussed the recent results of carbohydrate-based antimicrobial agents developed by our group. Other excellent works by other scientists and possible directions in the future are also discussed.     

Determination of d(+)glucose, d(+)mannose, d(+)galactose or d(-)fructose in a mixture of hexoses and pentoses by use of dental plaque coupled with a glass electrode

A potentiometric sensor has been developed by coupling dental plaque with a flat-surface glass electrode. Selectivity of this electrode for hexoses and pentoses has been tested. The electrode responds linearly to beta-d(+)glucose, d(+)mannose, d(+)galactose and beta-d(-)fructose over a narrow concentration range between 10(-4) and 10(-3)M, but has negligible response to the other hexoses and pentoses. This "plaque" electrode, using live bacterial cells, may serve as a model for the development of other selective electrodes for carbohydrates.     

Total determination of metal-binding carbohydrates in plant extracts by using FIA with electrochemical detection

FIA with pulsed amperometric detection (PAD) is used for the determination of metal-binding carbohydrates in plant extracts. Results of direct FIA measurements agree very well with those of corresponding HPLC-PAD analyses. The proposed method is used to determine total carbohydrates in isolated low-molecular-weight fractions of plant roots, which have been obtained after extraction at different pH values. The results are compared with those obtained by corresponding metal determinations (Ca, Mg, Zn, Mn) by AAS and also with constant potential amperometric detection at a copper working electrode. The latter detection mode is more sensitive, but less selective for carbohydrates. Received: 12 January 2000 / Revised: 2 March 2000 / Accepted: 4 March 2000     

Determination of sugars by liquid chromatography with post-column catalytic derivatization and fluorescence detection

Summary A method for the determination of reducing sugars such as fructose and glucose and nonreducing sugar such as sucrose by high performance liquid chromatography followed by an acidic hydrolysis and a derivatization with benzamidine has been developed. After separation of sugars on a gel column packed with a polymer-based cation exchange material (Sugar-Pak I, Waters-Millipore), the sucrose is first hydrolysed in a solid phase reactor to convert it into reducing subunits. A post-column fluorigenic reaction with benzamidine under alkaline condition allows the selective determination of both natural and converted reducing carbohydrates.This procedure has proven to be selective (fluorigenic detection) and highly sensitive (allowing detection as little as picomoles amounts), reproducible and linear over a broad range of concentrations: 5×10^–4 to 1.0×10^–2 M.The applicability of this method to natural matrices such as plant extracts and beverages is also described. The sugar content of a barley extract has been determined and compared with a specific enzymatic test. The determined sugar content of natural and commercial lemon juices as well as of Cola beverages has been compared with those found by the conventional LC refractive index analytical procedure. In all cases, the results were comparable and were within the experimental errors of the methods.     

单糖脱水制备呋喃类化合物的研究进展

随着社会的发展,人类对能源的需求越来越多,但是地球上化石资源的储藏量逐渐减少,不可再生资源正面临枯竭,对人类的生存提出了挑战,寻找开发新型能源已迫在眉睫．众所周知,绿色化学。代表了当今化学工业的发展方向;绿色化学希望化合物的来源是绿色的,即源于那些可再生资源;其生产工艺环境友好,     

Single‐Molecule Fluorescence Detection of a Synthetic Heparan Sulfate Disaccharide

The first single‐molecule fluorescence detection of a structurally‐defined synthetic carbohydrate is reported: a heparan sulfate (HS) disaccharide fragment labeled with Alexa488. Single molecules have been measured whilst freely diffusing in solution and controlled encapsulation in surface‐tethered lipid vesicles has allowed extended observations of carbohydrate molecules down to the single‐molecule level. The diverse and dynamic nature of HS–protein interactions means that new tools to investigate pure HS fragments at the molecular level would significantly enhance our understanding of HS. This work is a proof‐of‐principle demonstration of the feasibility of single‐molecule studies of synthetic carbohydrates which offers a new approach to the study of pure glycosaminoglycan (GAG) fragments.