Wyniki wyszukiwania - BazTech

1

Synteza polihydroksyindolizydyn z L,B-nienasyconych [delta]-laktonów

Rabiczko J., Socha D., Jurczak M., Chmielewski M.

Wiadomości Chemiczne

|

2002

|

[Z] 56, 7-8

561-583

EN

The isolation, synthesis and biological properties of polyhydroxylated alkaloids (iminosugars) constitute a well-visible trend in organic chemistry nowadays. Due to their structural resemblance to sugars, iminosugars are recognized by glycosidases, the enzymes that catalyse the hydrolysis of glycosidic bonds in carbohydrates and glycoconjugates. Since glycosidases play a very important role in many biological systems, the iminosugars which inhibit them display interesting biological activities. Indolizidines represented by castanospermine, swainsonine and lentiginosine are particularly interesting as they exhibit a variety of important biomedical properties. The present paper is not a survey of the literature, but only deals with syntheses towards lentiginosine, with the aim of illustrating representative approaches in the syntheses of polyhydroxyindolizidines. The high stereoselectivity of both the conjugate addition of hydrazine and the (1,3)-dipolar cycloaddition of nitrones to the a,b-unsaturated sugar d-lactones, prompted us to use the adducts of both reactions as substrates for the syntheses of polihydroxyindolizidines. The conjugate addition offers a stereocontrolled entry to derivaties of both D- and L-2-pyrrolidineacetic acids which can be easily transformed into desired indolizidines. As an example, the syntheses of lentiginosine are demonstrated. The (1,3)-dipolar cycloaddition of Brandi's nitrone to the title lactones proceeded with high stereoselectivity in the case of D- and L-glycero lactones, whereas there was a high kinetic resolution in the case of racemic D,L-glycero lactone. It was shown that adducts can be easily transformed into lentiginosine, 7-hydroxylentiginosine and 7,8-dihydroxylentiginosine.

2

Synteza glikozydów, disacharydów i pseudodisacharydów w reakcjach z udziałem związków palladu

Kryczka B., Porwański S.

Wiadomości Chemiczne

|

2002

|

[Z] 56, 7-8

627-660

EN

Carbohydrates are found in nature in variety of forms, in chemical association with a vast number of compounds, including other sugars, and in materials which perform a range of functions varying from structural to specifically functional in many biochemical ways. The attachment of monosaccharide units to other molecules proceeds usually through the anomeric centre by O-, N-, S- or C-glycosidic bond. Most synthetically useful glycosylation reaction is nucleophilic displacement at the anomeric centre. It occurs through glycosyl cations, usually from activated leaving groups in suitable glycosyl derivatives, most frequently halides and imidate esters. There are so many variables involved in glycoside and disaccharide synthesis that each target compound requires a particular strategy. That is why so many procedures have been developed to provide the regio- and stereocontrol in the glycosylation step. However, these methodes have been known for many years-and still modified-the selective synthesis of glycosides still determines the main challenge in the chemistry of carbohydrates. The aim of this paper is to present the role of palladium-catalyzed methodology in glycosylation reactions. The Heck reaction has been applied first by Daves and Czernecki to C-glycosidic synthesis. Reaction of glycals with various reagents offering nucleophilic carbon centres in the presence palladium-catalyst, affords important means of acces to 2,3-unsaturated C-glycosides. The popularity of this methodology started to flourish when it was found that it was able to control the selectivity by using certain reaction procedures to give fairly predictible results. Allylic carbonates are well-known compounds that undergo a variety of palladium-catalyzed reactions. This methodology has been applied to synthesis of many alkenyl glycosides. The reaction proceeds under neutral and very mild conditions and usually gives only one anomer. The same methodology was extended to the preparation of C-, N-, and S-glycosides as well as unsaturated di- and trisaccharides (Scheme 31), [86, 93]. These products are obtained in good yields by alkylation of ethyl a-O-D2-glycosides, having a leaving group at C-4, with C-, N-, S-nucleophiles, with various carbohydrates or with thiocarbohydrates. The reaction is regio- and stereoselective for the a-erytro enoside, and only stereoselective for a-threo enoside.

3

Struktura chemiczna, swoistość antygenowa i znaczenie w chorobotwórczości lipopolisacharydu (LPS, endotoksyna) na przykładzie bakterii Proteus vulgaris

Różalski A., Torzewska A., Bartodziejska B., Babicka D., Kwil I., Perepelov A.V., Kondakova A.N., Senchenkova S.N., Knirel Y., Vinogradov Evgeny V.

Wiadomości Chemiczne

|

2002

|

[Z] 56, 7-8

585-604

EN

Gram-negative bacteria of the genus Proteus from the family Enterobacteriaceae are opportunistic pathogens, which cause mainly wounds and urinary tract infections (UTI), the latter leading to severe complications, such as acute or chronic pyelonephrithis and formation of bladder and kidney stones. Virulence factors and properties of Proteus sp. mediating infectious process are swarming phenomenon, adherence due to the fimbriae or glycocalyx, flagella, invasiveness, urease, amino acids deaminases, proteases, hemolysins, capsular polysaccharide (CPS), and lipopolysaccharide (LPS). LPS is an integral component of cell wall of bacteria. It also represents the endotoxin which, after being released from bacterial cells, causes a broad spectrum of pathological effects leading in severe cases to the septic shock. Lipopolysaccharide consists of three parts - O- specific chain (O-antigen), core and lipid A; all of them have been studied in Proteus LPS. It has been documented that Proteus is an antigenically heterogeneous genus, principally because of structural differences in its O-specific polysaccharide chain of LPS. The serological classification of P. mirabilis and P. vulgaris shares 60 serogroups : 22 described for P. vulgaris, 33 characteristic for P. mirabilis and 5 common for both P. mirabilis and P. vulgaris. Serological classification of Proteus penneri still remains to be completed. Proteus O-antigens are branched or linear polysaccharides, built up of oligosaccharide repeating units, varying from a trisaccharide to a hexasaccharide. Acidic O-specific polysaccharides represent the majority of Proteus O-antigens; it was found that 80% of Proteus O-antigens were acidic. Uronic acids and amino sugars usually determine the serological specificity of Proteus O-antigens. Amino sugars in Proteus O-antigens are usually N-acetylated. In many O-antigens, sugars constituents carry an O-acetyl groups. Hexuronic acids either have free carboxyl group or are amidated with the a-amino group of amino acids - lysine, serine, alanine or threonine. Chemical and serological studies have been undertaken with the aim to understand on the molecular level the immunospecificity of Proteus LPS and its potential role during infection of bacteria. The O-antigens and O-antisera against Proteus with defined epitope specificity can be used for serodiagnosis and epidemiological studies. It was found that O-specific polysaccharide Proteus bacteria is involved in creation of glycocalyx which allows bacteria to grow in microcolony or in biofilm. Biofilm protects bacteria against action of antimicrobial agents and leukocytes, and it is also a organic gel-like surrounding contributing to stone formation. LPS from the S form of bacteria, containing all three regions also contributes to their resistance against bactericidal action of serum. The present review is mainly focused on the structure, specificity and biological function of Proteus vulgaris LPS.

4

O czwartorzędowych solach N-glikopiranozyloamoniowych

Dmochowska B., Skorupowa E., Wiśniewski A.

Wiadomości Chemiczne

|

2002

|

[Z] 56, 7-8

679-690

5

Glikozylacja z zastosowaniem pochodnych 1-tiocukrów jako substratów

Szeja W., Bugla J., Niemiec A., Pastuch G., Kasprzycka A., Ślusarczyk A., Wandzik I., Bieg T., Przybysz B., Bogusiak J.

Wiadomości Chemiczne

|

2002

|

[Z] 56, 7-8

605-625

EN

It was found that carbohydrate part of complex glycosides may act as antigens or receptors for proteins, and these findings led to the discovery of the important role of carbohydrates in cell-cell recognition phenomena and cell differentiation. At the same time the methods of glycosylation underwent rapid development. The present paper gives an overview of development of 1-thiosugar derivatives in oligosaccharide synthesis. In the first part of this review, recent results of the use of thioglycosides, dithiocarbonates, dithiocarbamates and thiophosphates as glycosyl donors and acceptors are presented. A survey of important methods for the synthesis of thiosugars is presented, followed by discussion of methods converting anomeric substituent into a good leaving group (activation) in nucleophilic substitution reaction. The mechanism and procedures, which provide stereoselective formation of 1,2-cis and 1,2-trans glycoside bond, are discussed. The versatility of 1-thiosugar derivatives in synthetic carbohydrate chemistry is illustrated by selective activation strategies. The most important synthetic methodologies of the synthesis of oligosaccharides like linear glycosylation strategy in step-by-step and multistep "one-pot" sequence, "armed-disarmed" glycosyl donor, "latent-active" glycosylation, orthogonal strategy are illustrated on several examples. The last part is devoted to methods for solid support oligosaccharide synthesis.

6

Allilocynowe pochodne cukrów prostych w syntezie układów karbocyklicznych

Jarosz S., Skóra S., Szewczyk K.

Wiadomości Chemiczne

|

2002

|

[Z] 56, 7-8

661-678

EN

Sugar allylic alcohols of the general formula Sug-CH=CH-CH2OH are easily converted into the allyltin derivatives Sug-CH=CH-CH2SnBu3 (7) by conversion into xanthate followed by its thermal rearrangement and subsequent SR2' reaction of resulting thiocarbonate with tri-n-butyltin hydride. Allyltin derivatives 7 undergo a controlled rearrangement with zinc chloride to dienoaldehydes CH2=CH-CH=CH-CH(OR)3CHO with the trans geometry across the internal double bond (3-E). Dienoaldehydes 3-E react with the C2-Wittig-type reagents [phosphoranes: Ph3P=CH-COR or phosphonates: (MeO)2P(O)CH2COR] to afford trienes 18 [CH2=CH-CH=CH-CH(OR)3CH=CH-C(O)-R), which undergo the intramolecular Diels-Alder reaction to give optically pure highly oxygenated bicyclo[4.3.0]indene derivatives 5 with the trans junction between the five and six-membered rings. Alternatively, the dienoaldehyde 3-E can be converted into - regioisomeric to 18 - triene 24 [CH2=CH-CH=CH-CH(OR)3C(O)-CH=CH-R], cyclization of which furnish optically pure bicyclo[4.4.0]decane derivatives 4 with the cis junction between both six-membered rings. On the other hand, sugar allylic bromides react with with tri-n-butyltin cuprate to afford a mixture of the primary and secondary allyltin derivatives [Sug-CH=CH-CH2SnBu3 (7) and [Sug-CH(SnBu3)-CH=CH2] (15) respectively]. Both isomers 7 and 15 might be converted into the trans dienoaldehyde 3-E by action of ZnCl2. However, thermal behavior of these regioisomers is different. The primary derivative 7 is stable up to at least 170 °C, while the secondary one (15) undergoes elimination of the tributylstannyl moiety already at 140 °C (boiling xylene) to afford dienoaldehyde with the cis-geometry across the internal double bond (3-Z). Such aldehyde was used for the preparation of - isomeric to 5 - derivative of bicyclo[4.3.0]indene with the cis-configuration between both rings (23). The stereochemistry of all these cyclizations might be rationalized assuming the endo-transition states of the intramolecular Diels-Alder reactions. Mechanism of the rearrangement of sugar allyltin derivatives 7 and 15 to unsaturated aldehydes 3-E and 3-Z is discussed.