Wyniki wyszukiwania - BazTech

1

Wybrane antybiotyki nukleozydowe

Samaszko-Fiertek J., Dmochowska B., Ślusarz R., Madaj J.

Wiadomości Chemiczne

|

2017

|

[Z] 71, 1-2

15--32

EN

Every year there has been a growing increase in infections caused by strains of bacteria resistant to multiple drugs. This prompts scientists to search for new antibiotics that would be able to fight these infections. New therapeutics used in medicine, which offer greater hopes are nucleoside antibiotics. They represent a large family of natural compounds exhibiting a variety of biological functions [1]. These include antifungal, antiviral, antibacterial, insecticides, immunosuppressants or anticancer properties. These broad-spectrum antibiotics can be divided into three main groups: • antibacterial nucleoside antibiotics, responsible for the inhibition of bacterial translocation of phospho-N-acetylpentapeptides, involved in the biosynthesis of peptidoglycan cell wall of bacteria; • antifungal nucleoside antibiotics, which role is to inhibit chitin synthase, or stopping construction of the cell wall of fungi; • antiviral antibiotics nucleoside, their mechanism of action is mainly based on blocking the biosynthesis of proteins by peptide inhibition transferase. In recent years much attention has been focused on the construction, mechanism of action and biosynthesis of antibiotics [1–3]. The development of genetic engineering has opened the way for combinatorial biosynthesis and obtaining new or hybrid compounds. In this work we would like to discuss some of bioactive naturally occurring nucleoside antibiotics, such as tunicamycin (Fig. 6) [19–22], mureidomycin (Fig. 8) [31–34], muramycin (Fig. 9) [36] or capuramycin (Fig. 10) [38].

2

D-Rybono-1,4-lakton. Część 2, Wykorzystanie w syntezie organicznej – wybrane reakcje

Madaj J., Samaszko-Fiertek J., Ślusarz R., Dmochowska B.

Wiadomości Chemiczne

|

2017

|

[Z] 71, 11-12

861--885

EN

There are many examples of syntheses with d-ribono-1,4-lactone as a substrate. Among all, its biggest advantage is undoubtedly its accessibility. It can be synthesized on a large scale from naturally available raw materials. Its characteristic feature is the stable configuration of individual carbon atoms in multiple reaction conditions. Very important is the presence of a carbonyl moiety, allowing for a variety of additions which is crucial for carbon-carbon bond formation, the most difficult synthesis in organic chemistry. In this article we present selected examples of articles that were published after 1984. In this year, the second article describing the Use of d-Ribonolactone in Organic Synthesis [36] was published. After this time many articles describing the use of the entitled lactone as a substrate in organic synthesis were published. We thought it would be worthwhile to present in Polish a selection of them. C-Glycosides and nucleoside analogs are a particularly important type of synthesized products. Examples of their synthesis are presented in this work, namely, neplanocin A [5], B [31] and F [24], citreovirdin [14], 2-bromopyridin α- and β-d-ribofuranosides [10], 4-deazaformicin A [27] and varitriol [ 33].

3

D-Rybono-1,4-lakton. Część 1, Otrzymywanie i wybrane pochodne

Madaj J., Samaszko-Fiertek J., Ślusarz R., Dmochowska B.

Wiadomości Chemiczne

|

2017

|

[Z] 71, 11-12

844--859

EN

Sugars are extremely important chiral substrates in organic synthesis. Thanks to the possibility of obtaining them from natural sources, their prices are relatively low which increases their attractiveness. d-Ribono-1,4-lactone is included in these compounds. For years it has enjoyed great interest as a substrate. In the early 1980’s two review articles were published in reputable journals [4, 5]. It has been a long time since these articles were published so we have decided to prepare a more up- -to-date review article in Polish. d-Ribono-1,4-lactone can be synthesized in many ways. The most interesting way seems to be the oxidation with KMnO4 [9] or molecular Br2 [10]. The use of bromine may appear to be harmful to the environment. That is why the search for more environmentally friendly methods is ongoing. However, the new methods are not as sufficiently satisfactory and often more expensive than the conventional, previously named methods. Therefore, the most commonly used method is the oxidation of D-ribose with molecular bromine. Very important derivatives of d-ribonolactone are acetal derivatives: 2,3-O-isopropylidene [10, 16] and 3,4-O-benzylidene derivatives [17]. They are often the starting materials for further synthesis. In the case of the latter compound the proper structure was determined by crystallography many years after its synthesis [18]. Very important group of derivatives are derivatives modificated at C-5: sulphonic [21], fluorine [22], chlorine [23], bromine [16, 24], azide [25] and phosphate [27]. Especially important are 5-bromo-5-deoxy derivatives. Examples of their use for the synthesis of thioalditols and thiosugars are described in the literature. It is also worth mentioning the possibility of synthesis of 1,2-unsaturated [28–30] and 2,3-unsaturated [31] derivatives. Presented examples of derivatives prove that using a d-ribono-1,4-lactone a whole range of derivatives extremely useful for further synthesis of more complex compounds can be obtained.

4

Alditole i anhydroalditole

Sikora K., Samaszko-Fiertek J., Ślusarz R., Liberek B., Madaj J., Dmochowska B.

Wiadomości Chemiczne

|

2017

|

[Z] 71, 1-2

65--86

EN

Alditols belong to the group of acyclic polyols. Formally, they are obtained from the aldose or ketose by reduction of the carbonyl group. Single or double dehydratation of alditols provides the cyclic compounds named anhydroalditols and dianhydroalditols, respectively. Alditols and anhydroalditols are widespread in both animal and plant kingdoms. They are in human blood and urine, and in the amniotic and cerebrospinal fluids. Herein the applications of alditols and anhydroalditols in medicine and human nutrition are presented. (For example d-mannitol is used as a diuretic agent or in osmotherapy to reduce acutely raised intracranial pressure; isosorbide mononitrate is used against angina pectoris. Xylitol (pentitol) can counteract several diseases, among others, the acute otitis media, osteoporosis, tooth decay and helps the remineralization of teeth, thanks to that it found use as an additive to chewing gum [4]. Most alditols including d-mannitol, d-glucitol and 1,4-anhydro-d,l-galactitol, are used as sweeteners and as well as additives for low caloric food or as diets for diabeties. Although they show lower sweetness than glucose or saccharose, their great advantage is that it does not cause a rapid increase of glucose level in blood [5,6]. While nitrates 1,4:3,6-dianhydro-d-mannitol and 1,4:3,6-dianhydro-d-glucitol thanks to the ability of blood vessels relaxant are commonly used for years in the treatment of heart diseases and blood system [10]). It is demonstrated that introduction of alditol or anhydroalditol to biologically active compound may improve its activity. Anhydroalditols are also useful substrates for the stereospecific synthesis of bicyclic compounds. Additionally, alditols and anhydroalditols are promising monomers for synthesis of polymers with interesting properties. Finally, methods of alditols and anhydroalditols syntheses are presented. Among them we consider: cyclization in an acid medium involving intramolecular dehydration, SN2 reaction with suitable leaving groups, deamination reaction combined with reduction, reduction of glycosyl halide, tioglycoside and glycoside, and addition of water or hydrogen to the double bond in glycals.

5

Rutyna : budowa, właściwości

Samaszko-Fiertek J., Roguszczak P., Dmochowska B., Ślusarz R., Madaj J.

Wiadomości Chemiczne

|

2016

|

[Z] 70, 7-8

435--453

EN

Flavonoids commonly can be found in plants. They protect them against various microorganisms or insects [1]. Flavonoids demonstrate not only antioxidant properties, but also prevent the development of cancer [2]. This is attributed to their ability to induce apoptosis of tumor cells. The structure of this type of compound is based mainly on the flavone skeleton with the keto group in position 4 (Fig. 2). The difference in structure of flavonoids consists mainly in the number and nature of the substituents. Flavonoid compounds have a 15-carbon atoms skeleton, consisting of two aromatic rings (A and B) connected to 3 carbon atoms, by oxygen contained within the heterocyclic ring C (Fig. 2) [5]. Structural difference of the pyranose ring C and position of the phenyl ring B are the basis for the division flavonoids into seven groups (Fig. 3) [6]. In recent years a number of work focused on the study of flavonoids complexes with ions of copper(II) or iron(II) were published [20–22]. One of the most important flavonoids is rutoside, which has a number of important biological activities. One of the most important function of this compound is inhibition hyaluronidase activity by reducing the permeation and improveing the flexibility of blood vessels. It is used to treat diseases such as diabetic retinopathy, inflammation of the mucous membranes of the nose, atherosclerotic diseases or disorders of the venous circulation. Rutoside forms a relatively stable complex with ions of iron(II) or calcium(II) as well as nickel(II) and especially with copper(II). This type of complex protect from rapid degradation/oxidation of L-ascorbic acid [14, 15]. In 2011, Sak-Bosnar and colleagues proposed the structure of rutoside complex with ions of copper (II) (Fig. 9) [20]. In the same year was published work suggesting that a key role in this type of mechanism play hydroxyl group at the 3 ‚carbon atom, which becomes a „carrier” of the electron/radical (Fig. 5) [19].

6

Metody określania struktury polisacharydów

Samaszko-Fiertek J., Kuźma M., Dmochowska B., Ślusarz R., Madaj J.

Wiadomości Chemiczne

|

2016

|

[Z] 70, 5-6

299--318

EN

Sequencing of polysaccharides is difficult to achieve because of the heterogeneous nature of the polysaccharide structure, high molecular weight (the size of a polysaccharide varies between approximately 16,000 and 16,000,000 daltons (Da)), and polydispersity of the polymer chains. The following information is essential to determine the primary structure of a polysaccharide: • monosaccharide composition: nature and molar ratios of the monosaccharide building blocks; • relative configuration of monosaccharides: d or l; • anomeric configuration: α- or β-configuration of the glycosidic linkage; • ring size: presence and distinction of furanosidic and pyranosidic rings; • linkage patterns: linkage positions between the monosugars and branches; • sequences of monosaccharide residues in the repeating units; • substitutions: position and nature of OH–modifications, such as O–phosphorylation, acetylation, O-sulfation, etc.; • molecular weight and molecular weight distribution. A polysaccharide extracted from plant materials or food products is usually purified before being subjected to structural analysis. The first step of characterizing a polysaccharide is the determination of its purity, which is reflected by its chemical composition, including total sugar content, level of uronic acids, proteins, ash, and moisture of the preparation. The second step is the determination of monosaccharide composition, which will unveil structural information such as the number of monosaccharides present in the polysaccharide and how many of each sugar unit. NMR spectroscopy has become the most powerful and noninvasive physicochemical technique for determining polysaccharide structures. It can provide detailed structural information of carbohydrates, including identification of monosaccharide composition, elucidation of α- or β-anomeric configurations, establishment of linkage patterns, and sequences of the sugar units in oligosaccharides and/or polysaccharides. Monosaccharide composition can be determined also by analysis of totally acid hydrolyzed polysacharide using high performance liquid chromatography (HPLC) or gas chromatography (GC). The ring size and glycosidic linkage positions of sugar units in a polysaccharide could be established by methylation analysis and/or cleavage reduction. The anomeric configuration is conventionally determined by oxidation, and this method can be combined with mass spectrometry to obtain more structural information.

7

Egzopolisacharydy bakteryjne : budowa i funkcje

Samaszko-Fiertek J., Kuźma M., Dmochowska B., Ślusarz R., Madaj J.

Wiadomości Chemiczne

|

2016

|

[Z] 70, 7-8

473--496

EN

Exopolysaccharides fulfil protective functions and allow bacteria live in the communities, single or mixed, by facilitating adhesion to surfaces and to each other. Microbes prefer to exist in the form of a biofilm. The term biofilm was introduced in 1978 and is the group of microorganisms surrounded by extracellular, highly hydrated mucus, which allows adhesion on various surfaces and adhesion of cells to each other [1]. The extracellular slime owes its character mainly due to the presence of exopolysaccharides. Bacteria living in biofilms, have a high resistance to external factors, such as changes in temperature, pH, humidity, oxygenation, presence of bacteriocins, antibodies or antibiotics. They may be up to 1,000 times more resistant to antibiotics than planktonic forms. They can be synthesized inside and outside bacteria cell. The structure of the bacterial exopolysaccharide is very diverse, but very often, due to the presence of uronic acid residues, or non-sugar organic acids as pyruvic acid, succinic acid, as well as residues of inorganic acids such as phosphoric acid or sulfuric acid, they are negatively charged particles. In addition, a characteristic of most of the exopolysaccharides (EPS) is their enormous molecular mass of up to several million g/mol [11]. Thanks to its rheological properties, ease of isolation, and often biodegradable antioxidant activity extracellular polysaccharides are increasingly used in industry as a gelling agents, hardening and thickening agents, emulsifiers, food coatings and pharmaceutical products. In addition, they can be used as bandages, anti-cancer agents, cholesterol-lowering, antiulcer or immunomodulators [20–27]. This article discusses in details the selected exopolysaccharides such as xanthan, gellan, exopolysaccharides of lactic acid bacteria, dextran, bacterial cellulose, alginic acid, hyaluronic acid, mannans.

8

Cukrowe czwartorzędowe sole amoniowe

Dmochowska B., Sikora K., Samaszko-Fiertek J., Ślusarz R., Madaj J.

Wiadomości Chemiczne

|

2016

|

[Z] 70, 7-8

497--518

EN

Quaternary ammonium compounds (QACs) exhibit the properties of both inorganic and organic compounds, and their ionic nature gives them hydrophilic character. The popularity of these compounds is allied to their many applications and ease of synthesis. Most of QACs are stable up to 150°C, readily soluble in water, usually non-toxic in utilitarian concentrations, are surface active, and do not irritate the skin or have a noxious odour [1]. Many of them have fungicidal, bactericidal and algicidal properties [2–5]. The antiviral action of QACs, including against HIV [6, 7], has been reported. They are used as timber preservatives, disinfectants, fabric softeners, anti-electrostatic agents and antifriction substances [5, 8, 9]. In addition, certain drugs administered in cases of diabetes, cardiac arrhythmia, neuroses, allergies and even carcinomas are QACs. Finally, QACs are used in chemical synthesis as catalysts, in phase-boundary catalysis [11], in the reduction of aldehydes and alkenes, and in the Friedl-Crafts reaction. In literature there is only limited amount of information considering quaternary ammonium salts containing sugar substituents. Among them four group of compounds arises: salts linked to C6 atom in sugar, directly connected to anomeric carbon atom, linked trough hydrocarbon spacer and derivatives of polisacharides. Kirk at al. described the synthesis of biologically active QACs [15]. In the Menshutkin reaction between an iodo-derivative and trimethylamine (Scheme 4), these authors obtained compounds with bactericidal and fungicidal properties. The authors obtained a series of analogous compounds using carboxylic acids (with carbon chains of various lengths) ester linked to the C-6-OH group of a sugar derivative. Blizzard synthesized QAC derivatives of vancomycin [28]. It was noticed that the increased hydrophilicity of vancomycin following the addition to it of a suitable fragment enhanced its antibacterial properties [30, 31], one of the more active being a derivative containing an aminium group at position G-6 (Scheme 10). Examples of reactions, in which the terminal carbon atoms in methyl glucopyranosides and polysaccharides are functionalized, are the syntheses carried out by Engel et al. [33, 34], one of which is shown in Figure 5. These authors aimed to find compounds with antibacterial properties. In the first instance, the hydroxyl groups at atoms C-6 of the sugar units in cellulose were O-tosylated. Then, the terminal carbons were functionalized with tertiary amines, yielding QACs. The most effective bactericide among these compounds was the one with a 16-carbon chain, the structure of which is shown Figure 6.

9

Peptydoglikan : budowa, rola biologiczna oraz synteza

Samaszko-Fiertek J., Dmochowska B., Madaj J.

Wiadomości Chemiczne

|

2015

|

[Z] 69, 7-8

513--540

EN

The most important component of bacterial cell walls especially Gram-positive bacteria is peptidoglycan, called also murein, PGN. The first time this synonym was used in 1964 by Weidel and Pelzer [1]. Peptidoglycan is present in the outer layer of the cytoplasmic membrane and its structure. The structure of peptidoglycan depends on the bacteria strain. It is estimated that in Gram-negative bacteria, it occupies only about 10–20% of the total area of the cell wall, when in Gram-positive bacteria it is 50 and up to 90% of all space. Problems with isolation with high purity of biological material shows the need for developing techniques for chemical synthesis of peptidoglycan fragments and their analogs. In past few years there has been a growing interest within the synthesis of compounds glycoprotein (glycopeptides, peptidoglycan, etc.). As a basis for the construction of cell walls of many bacteria. Despite intensive research and gain significant knowledge of the physical and biological, chemical synthesis or biosynthesis (Fig. 5 and 6) of peptidoglycan, not so far failed to unambiguously determine its three-dimensional structure. The works of Kelman and Rogers [15] and Dimitriev [20] nearer picture of its structure. However, the time to develop in vivo visualization of cell structure it will be difficult to identify correctly peptidoglycan three-dimensional structure. Due to the important biological roles of murein, many research centers have taken to attempt their chemical synthesis. For biological research began to use chemically synthesized peptidoglycan fragments which guaranteed both uniform and a certain structure. An important roles in the development of methods of chemical synthesis of peptidoglycan had H. Chowdhury work, Fig. 8 [35], Hesek, Fig. 9 and 10 [36, 37], Dziarskiego [38] and Boneca [39] and Inamury [34, 40].

10

Badanie oddziaływania wankomycyny z fragmentem peptydoglikanu ściany komórkowej bakterii

Samaszko-Fiertek J., Ślusarz R., Madaj J.

Wiadomości Chemiczne

|

2015

|

[Z] 69, 7-8

491--511

EN

Unfortunately, despite of work involved in understanding of the mechanism of bacterial virulence, especially Staphylococcus aureus, it has not been developed effective therapy against this bacteria. The first antibiotic used against this bacteria was penicillin, which was discovered by Alexander Fleming in 1928. A new generation of drugs introduced into therapy against Staphylococcus aureus and other Gram-positive bacteria are glycopeptide antibiotics. The most widespread and most commonly used are vancomycin and teicoplanin, discovered respectively in 1956 and 1978. As a result of frequent use of vancomycin VISA (ang. Vancomycin-intermediate Staphylococcus aureus) and VRSA (ang. Vancomycin-resistant Staphylococcus aureus) strains were discovered. The mechanism of action of this antibiotic based on the inhibition of the biosynthesis of bacterial cell wall peptidoglycan fragment. Forming stabilized by hydrogen bonds complex with terminal fragment of peptidoglycan (dipeptide d-Ala-d-Ala) vancomycin prevents its further crosslinking [2] (Fig. 1). However, in recent years other theories of the mechanism of action of glycopeptide antibiotics against Gram-positive bacteria were presented it seems to be crucial to find methods of selection of new antibiotics and for this purpose standard techniques of the analysis, including isothermal titration calorimetry (ITC) [3], nuclear magnetic resonance spectroscopy (NMR) [8–15], high performance liquid chromatography (HPLC) [16], capillary electrophoresis [17] or self-assembled monolayers (SAMs) [22] are used. Discovering new methods for studying of interaction between vancomycin and Gram-positive bacterial cell wall allows use it as a new technique for rapid selection of potential new antibiotics, including glycopeptide derivatives.