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Über dieses Buch

This second edition is a short and comprehensive study on the best known approaches for preparing the main types of glycosides. It covers synthetic pathways of challenging glycosides known as antiviral or antineoplastic drugs, and synthetic substrates used for enzymatic detection, including those used for detection of gene markers in plant biotechnology. The author pays special attention to the structural characterization of glycosides and provides the basic tools for the structural assignment through NMR, X-Ray and mass spectra techniques. The book also covers strategies for preparation of antiviral and antineoplastic drugs included in a drug design course.

Inhaltsverzeichnis

Frontmatter

Chapter 1. Glycosides, Synthesis and Characterization

Abstract
Monosaccharides are generally defined as aldoses and ketoses connected to a polyhydroxylated skeleton [1]. In an aqueous solution, monosaccharides are subject to internal nucleophilic addition to form cyclic hemiacetal structures. When addition occurs between -OH at C(4) or -OH at C(5), and the carbonyl group, a five- or a six-member ring is formed called a furanose or a pyranose respectively. It is also known that an equilibrium exists between the open and the cyclic form, being displaced to the latter by more than 90 %. Therefore, in aqueous solution, it is more accurate to consider that most sugars are present as cyclic molecules and behave chemically as hemiacetals.
Marco Brito-Arias

Chapter 2. O-glycoside Formation

Abstract
When a monosaccharide (or a sugar fragment of any size) is condensed with either an aliphatic or aromatic alcohol, or another sugar moiety through oxygen, a glycoside bond is formed. General examples of -glycosides are shown in Scheme 2.1.
Marco Brito-Arias

Chapter 3. N-glycosides

Abstract
N-glycosides are generated when a sugar component is attached to an aglycon, through a nitrogen atom, establishing as a result a C–N–C linkage. Nucleosides are among the most relevant N-glycosides since they are essential components of DNA, RNA, cofactors, and a variety of antiviral and antineoplastic drugs.
Marco Brito-Arias

Chapter 4. Nucleoside Mimetics

Abstract
Modified nucleosides are useful therapeutic agents being currently used as antitumor, antiviral, and antibiotic agents. Despite the fact that a significant variety of modified nucleosides display potent and selective action against cancer, viral and microbial diseases, the challenge still attracts full attention since most of them do not discriminate between normal and tumor cell and in viral infections resistant strains usually appear during the course of the treatment.
Marco Brito-Arias

Chapter 5. C-glycosides

Abstract
C-glycosides have attracted much attention, considering that many of them have demonstrated their effectiveness as therapeutic agents. The increasing significance of C-glycosides is that the conformational differences compared to O- or N-glycosides are minimal, and that they are resistant to enzymatic or acidic hydrolysis since the anomeric center has been transformed from acetal to ether [1]. A glycoside is defined as C-glycoside when what is supposed to be the anomeric carbon of a sugar is interconnected to the aglycon, generating a new C–C bond. According to Levy and Tang [2] the term C-glycoside describes those structures in which a common structural motifs the presence of carbon functionality at what would otherwise be the anomeric position of a sugar or derivative. Structurally C-glycosides can be constituted by aliphatic, or aromatic aglycon, and the sugar can be pyranose or furanose. A variety of natural product C-glycosides have been described. Examples of C-glycosides isolated from different plant genera or insects and characterized spectroscopically are: Carminic acid (cochineal), Aloin (Aloe vera), Scoparin (Cytisus scoparius), Saponarin (Saponaria officinalis), flavonoid phytoalexins such as Cucumerins (Cucumis sativus) and Naringenin (grapefruit), [3] C-glucosyl xanthones [4], and complex benzoquinone Altromycin B [5] (actinomycetes), among others (Scheme 5.1).
Marco Brito-Arias

Chapter 6. Glycoconjugates

Abstract
Carbohydrates covalently attached to proteins and lipids constitute three types of glycoconjugates: proteoglycans, glycoproteins, and glycolipids. Although in the first two cases the types of linkages are the same, chemically proteoglycans behave as polysaccharides and glycoproteins having much less carbohydrate content as proteins. The third important class of glycoconjugates, where carbohydrate residues are covalently attached to a lipidic component, has been classified into four types depending on the lipidic nature: glycoglycerol, glycosyl polyisoprenol pyrophosphates, fatty acid esters, and glycosphingolipids [1].
Marco Brito-Arias

Chapter 7. Hydrolysis of Glycosides

Abstract
The glycosidic bond might be degraded by chemical and/or enzymatic agents. Comparative studies revealed that chemical hydrolysis is nonspecific and on the other hand the enzymatic is regiospecific and stereospecific. The glycosides are chemically susceptible to acid conditions and only in some cases to basic conditions. In general the acid sensitivity is attributed to the sugar moiety and the basic non-stability to the aglycon nature.
Marco Brito-Arias

Chapter 8. Nuclear Magnetic Resonance of Glycosides

Abstract
Nuclear magnetic resonance (1H, 13C NMR), X-ray diffraction, and mass spectrometry are considered the most important analytical methods for structural elucidation. Characterization by means of 1H, 13C NMR, monodimensional and bidimensional spectroscopy is a powerful tool for structural assignment of simple and complex glycosides. Pioneering studies [1–4, 48–50] on simple monosaccharides were essential for understanding, through the chemical shifts and coupling constants, the conformational behavior of sugars.
Marco Brito-Arias

Chapter 9. X-Ray Diffraction of Glycosides

Abstract
X-ray crystallography is a powerful tool for obtaining molecular information regarding bond lengths, bond angles, hydrogen bond interactions, and torsion angles, which are necessary elements for understanding the conformation of glycosides. Improved diffractometers, faster computational processors, and mathematical programs have made possible the structural resolution of simple and complex substances of glycosidic nature particularly those with noncentrosymmetric space groups.
Marco Brito-Arias

Chapter 10. Mass Spectrometry of Glycosides

Abstract
High-resolution mass spectrometry has become another valuable tool for characterization of simple and complex glycosides. The method is based on the collision of a high-energy electron against a sample under study producing as result a cation radical fragment known as the molecular ion, which should match with the molecular weight of the molecule. The mass spectrum also registers a number of fragments with the most intense base peak assigned a relative intensity of 100. Mass spectrometry can be applied as high and low ionization experiments, the former the most suitable for glycosides electron impact and the latter for fast atom bombardment (FAB) and electrospray ionization routine experiments for characterization of glycosides. In terms of sensitivity of the measurement this instrumental method requires a small amount of sample, even in the order of nanogram quantities.
Marco Brito-Arias

Backmatter

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