Academic literature on the topic 'Dideoxy sugars'

The treatment of hexopyranosyl bromides, also activated at C6 (Br, OTs, OMs), with H2S/HCONMe2 under basic conditions gives rise to 1,6-dideoxy 1,6-epithio sugars. One such sugar has been further transformed into the synthetically useful 3,4-anhydro-1,6-dideoxy-1,6-epithio-β-D-galactose. The treatment of this epoxide with sodium azide and with cyclohexylamine is described. An analogous treatment of one doubly activated hexopyranosyl bromide with sodium hydrogen selenide has led to a novel 1,6-dideoxy 1,6-episeleno sugar which displayed interesting n.m.r. spectra. Finally, in an attempt to prepare 1,6-dideoxy 1,6-epidithio sugars, a tetraalkylammonium tetrathiomolybdate reagent was found to be the reagent of choice for converting doubly activated hexopyranosyl bromides into 1,6-dideoxy 1,6-epithio sugars.

Abstract Reaction of sugar triflates (1) and (2) with tert-butyl cyanoacetate in presence of sodium hydride affords the cyclopropanated sugars (3) and (4), followed by selective hydrolysis of the ester group to free acids (5) and (6), respectively. Couplings of (5) and (6) with protected glycine and L-alanine lead to cyclopropanated sugar amino acids (7-10). The coupling of 6 with benzyl 3,4-(“exo”-aminomethyl)methano-3,4-dideoxy-β-L-arabinopyranoside (11) fur­ nished benzyl 3,4-[(C-cyano-amido)methano-(benzyl 3,4-(“exo”-methylene)methano-3,4-di-deoxy-β-L-arabinopyranosido)]-3,4-dideoxy-β-L-arbinopyranoside (12), suggesting an “exo” orientation of the ester group in 3 and 4.

The reduction of 1,2:5,6-di-O-isopropylidene-3-O-(methylthio) thiocarbonyl-β-D-idose ,- talose, and -(3-2H) talose with tributyltin hydride and deuteride leads to the deoxy sugar and some deuterium-containing deoxy sugars. A modification of the normal procedure allows for reduction with tributyltin hydride generated in situ. As well, the reduction of some dithiocarbonates derived from glycosides of N-acetyl-D- glucosamine allows access to a variety of dideoxy and trideoxy sugars.

Five 19F-substituted glucose analogues were used to probe the activity and mechanism of the enzyme mutarotase by using magnetisation-exchange NMR spectroscopy. The sugars (2-fluoro-2-deoxy-d-glucose, FDG2; 3-fluoro-3-deoxy-d-glucose, FDG3; 4-fluoro-4-deoxy-d-glucose, FDG4; 2,3-difluoro-2,3-dideoxy-d-glucose, FDG23; and 2,2,3,3-tetrafluoro-2,3-dideoxy-d-glucose (2,3-dideoxy-2,2,3,3-tetrafluoro-d-erythro-hexopyranose), FDG2233) showed separate 19F NMR spectroscopic resonances from their respective α- and β-anomers, thus allowing two-dimensional exchange spectroscopy measurements of the anomeric interconversion at equilibrium, on the time scale of a few seconds. Mutarotase catalysed the rapid exchange between the anomers of FDG4, but not the other four sugars. This finding, combined with previous work identifying the mechanism of the anomerisation by mutarotase, suggests that the rotation around the C1–C2 bond of the pyranose ring is the rate-limiting reaction step. In addition to d-glucose itself, it was shown that all other fluorinated sugars inhibited the FDG4 anomerisation, with the tetrafluorinated FDG2233 being the most potent inhibitor. Inhibition of mutarotase by F-sugars paves the way for the development of novel fluorinated compounds that are able to affect the activity of this enzyme invitro and invivo.

ABSTRACTMethanococcus maripaludishas two surface appendages, archaella and type IV pili, which are composed of glycoprotein subunits. Archaellins are modified with an N-linked tetrasaccharide with the structure Sug-1,4-β-ManNAc3NAmA6Thr-1,4-β-GlcNAc3NAcA-1,3-β-GalNAc, where Sug is (5S)-2-acetamido-2,4-dideoxy-5-O-methyl-α-l-erythro-hexos-5-ulo-1,5-pyranose. The pilin glycan has an additional hexose attached to GalNAc. In this study, genes located in two adjacent, divergently transcribed operons (mmp0350-mmp0354andmmp0359-mmp0355) were targeted for study based on annotations suggesting their involvement in biosynthesis of N-glycan sugars. Mutants carrying deletions inmmp0350,mmp0351,mmp0352, ormmp0353were nonarchaellated and synthesized archaellins modified with a 1-sugar glycan, as estimated from Western blots. Mass spectroscopy analysis of pili purified from the Δmmp0352strain confirmed a glycan with only GalNAc, suggestingmmp0350tommp0353were all involved in biosynthesis of the second sugar (GlcNAc3NAcA). The Δmmp0357mutant was archaellated and had archaellins with a 2-sugar glycan, as confirmed by mass spectroscopy of purified archaella, indicating a role for MMP0357 in biosynthesis of the third sugar (ManNAc3NAmA6Thr).M. maripaludismmp0350,mmp0351,mmp0352,mmp0353, andmmp0357are proposed to be functionally equivalent toPseudomonas aeruginosawbpABEDI, involved in converting UDP-N-acetylglucosamine to UDP-2,3-diacetamido-2,3-dideoxy-d-mannuronic acid, an O5-specific antigen sugar. Cross-domain complementation of the final step of theP. aeruginosapathway withmmp0357supports this hypothesis.IMPORTANCEThis work identifies a series of genes in adjacent operons that are shown to encode the enzymes that complete the entire pathway for generation of the second and third sugars of the N-linked tetrasaccharide that modifies archaellins ofMethanococcus maripaludis. This posttranslational modification of archaellins is important, as it is necessary for archaellum assembly. Pilins are modified with a different N-glycan consisting of the archaellin tetrasaccharide but with an additional hexose attached to the linking sugar. Mass spectrometry analysis of the pili of one mutant strain provided insight into how this different glycan might ultimately be assembled. This study includes a rare example of an archaeal gene functionally replacing a bacterial gene in a complex sugar biosynthesis pathway.

ABSTRACT O-antigen variation due to the presence of different types of sugars and sugar linkages is important for the survival of bacteria threatened by host immune systems. The O antigens of Shigella dysenteriae type 7 and Escherichia coli O7 contain 4-(N-acetylglycyl)amino-4,6-dideoxy-d-glucose (d-Qui4NGlyAc) and 4-acetamido-4,6-dideoxy-d-glucose (d-Qui4NAc), respectively, which are sugars not often found in studied polysaccharides. In this study, we characterized the biosynthetic pathways for dTDP-d-Qui4N and dTDP-d-Qui4NAc (the nucleotide-activated precursors of d-Qui4NGlyAc and d-Qui4NAc in O antigens). Predicted genes involved in the synthesis of the two sugars were cloned, and the gene products were overexpressed and purified as His-tagged fusion proteins. In vitro enzymatic reactions were carried out using the purified proteins, and the reaction products were analyzed by capillary electrophoresis, electrospray ionization-mass spectrometry, and nuclear magnetic resonance spectroscopy. It is shown that in S. dysenteriae type 7 and E. coli O7, dTDP-d-Qui4N is synthesized from α-d-glucose-1-phosphate in three reaction steps catalyzed by glucose-1-phosphate thymidyltransferase (RmlA), dTDP-d-glucose 4,6-dehydratase (RmlB), and dTDP-4-keto-6-deoxy-d-glucose aminotransferase (VioA). An additional acetyltransferase (VioB) catalyzes the conversion of dTDP-d-Qui4N into dTDP-d-Qui4NAc in E. coli O7. Kinetic parameters and some other properties of VioA and VioB are described and differences between VioA proteins from S. dysenteriae type 7 (VioAD7) and E. coli O7 (VioAO7) discussed. To our knowledge, this is the first time that functions of VioA and VioB have been biochemically characterized. This study provides valuable enzyme sources for the production of dTDP-d-Qui4N and dTDP-d-Qui4NAc, which are potentially useful in the pharmaceutical industry for drug development.

ABSTRACT All of the 2,6-dideoxy sugars contained within the structure of chromomycin A3 are derived from d-glucose. Enzyme assays were used to confirm the presence of hexokinase, phosphoglucomutase, UDPG pyrophosphorylase (UDPGP), and UDPG oxidoreductase (UDPGO), all of which are involved in the pathway of glucose activation and conversion into 2,6-dideoxyhexoses during chromomycin biosynthesis. Levels of the four enzymes inStreptomyces spp. cell extracts were correlated with the production of chromomycins. The pathway of sugar activation inStreptomyces spp. involves glucose 6-phosphorylation by hexokinase, isomerization to G-1-P catalyzed by phosphoglucomutase, synthesis of UDPG catalyzed by UDPGP, and formation of UDP-4-keto-6-deoxyglucose by UDPGO.

2,3- Dideoxy sugars are versatile synthons for organic synthesis. The applications are diverse in biological systems and organic synthesis. In the first part of the thesis, 2,3-unsaturated sugars are used for the glycoconjugation of amino acids, peptides and proteins. In the later part, 2,3-dideoxy sugar is used to synthesize carbohydrate macrocycle. Finally, sugar vinyl sulfoxide is used to synthesize substituted pyran via 2,6- anhydro sugar formation. Chapter 1 of the thesis is divided into two parts. The first part describes the literature on unsaturated sugar, especially 2,3-unsaturated sugars, synthesis and their modifications. Attention is given to their addition reactions with nucleophiles and conjugation with biomolecules. A brief introduction to glycoconjugation is also reported in this part. Different glycoconjugation methods are discussed briefly, and the advantages are compared accordingly. The second part of this chapter elaborates on the synthesis of cyclic oligosaccharides. The approaches and the difficulties in the respective approaches are mentioned accordingly. Challenges with synthesising small cyclic oligosaccharides are cited according to the available literature. Current development in the field is also covered in the discussion. Chapter 2 of the thesis deals with the glycoconjugation methods using sugar vinyl sulfoxide involving Michael addition reaction. Glycoconjugations of amino acids, peptides and protein, namely lysozyme are demonstrated in benign physiological conditions. The smaller glycoconjugated molecules are characterized with the help of NMR spectroscopy and mass spectrometry, while the larger glycoconjugated peptide and protein are characterized with the help of mass spectrometry. Biophysical studies of glycoconjugated lysozyme showed increased stability in the presence of trypsin while retaining its antimicrobial activity. Thus, a benign glycoconjugation method is developed. Chapter 3 of the thesis unravels further potential of glycoconjugation using sugar vinyl sulfoxide. PETIM dendrimers of generation zero to three are glycoconjugated with sugar vinyl sulfoxide. The glycoconjugations of the lower generation dendrimers are confirmed using NMR spectroscopy and mass spectrometry; for higher generations, only NMR spectroscopy was employed for the characterization. The first-order reaction rate constant of the glycoconjugation reaction is also determined using NMR spectroscopy. Further biological evaluation of the native and glycoconjugated PETIM dendrimer reveals that PETIM dendrimers show selective antibacterial activity against M. smegmatis, and the native dendrimers show higher efficacy over the glycoconjugated dendrimer. Chapter 4 of the thesis describes the synthesis of the cyclic disaccharide molecule composed of 2,3-dideoxy furanoside monomer units. The synthesis started from protected glucal molecules and followed a few simple reaction steps, including the Ferrier reaction, desulfurization reaction, and selective hydroxy group protection and finally, glycoconjugation reaction. While the formation of the disaccharide is confirmed using NMR spectroscopy and mass spectrometry, the conformation of the constituting monomeric unit of the cyclic disaccharide is ascertained through solid state structure determination using the single crystal X-ray diffraction method. The ring contraction of the pyranoside monomer to furanoside cyclic disaccharide is explained by two plausible mechanisms involved in the glycosylation step. Further encapsulation property of the cyclic disaccharide molecule was evaluated against the 1-aminoadamantane using the ITC method. This experiment allows looking into the thermodynamics of the encapsulation and the encapsulation mode of the molecule. Chapter 5 of the thesis shows sugar vinyl sulfoxide's application and potential as a synthetic intermediate. Intra-molecular Michael addition reaction of the sugar vinyl sulfoxide in basic condition affords elusive 2,6-anhydro sugar molecules in a single step. Selective opening of the bicyclic ring of the anhydro sugar converts it to a substituted pyran. The applicability of this two-step, one-pot reaction is also tested on sugar vinyl sulfoxide derived from galactal. The thesis describes the achievement of the diversification of 2,3-unsaturated sugar. A benign glycoconjugation method is developed and adequately characterized. The synthetic potential of 2,3-dideoxy sugar is demonstrated through the synthesis of cyclic disaccharide via a ring contraction of pyranoside to a furanoside. And finally, a two-step reaction protocol converts pyranoside sugar into a substituted pyran.