The Role of the C-3 Substituent in the Asymmetric Dihydroxylation of Hexo-5-Enofuranosides

ABSTRACT

Asymmetric dihydroxylation of vinyl furanosides 1-6 by use of OsO₄, AD-mix-α® and β® is described yielding the corresponding hexofuranose sugars. Vinyl furanosides 2 and 3, with an ester group at C-3, and vinyl manno furanoside 5 on asymmetric dihydroxylation with AD-mix α® exhibited high R diastereoselectivity at C-5. Reversal in diastereoselectivity at C-5 was observed for the 3-deoxy vinyl furanoside 6 giving furanosaccharide 6S with the S configuration at C-5.     

Synthesis of Modified Di- and Trisaccharide Fragments of N-Glycoproteins

Abstract

The syntheses of several analogues of disaccharide Manot(1→6)Mana-OCH₃ (1) and of trisaccharide Mana(1→6)[Mana(1→3)]Mana-OCH₃ (2) are reported. The syntheses are described of the diastereomeric 6-methyl derivatives 9a and 9b, which are representatives of fixed conformations of disaccharide 1. The syntheses of the 2-amino-2-deoxy analogues 15 and 17 and the synthesis of the 2-fluoro-2-deoxy analogue 28 are also reported.     

Deoxygenation of sugar trifluoromethanesulfonates by sodium metal in liquid ammonia and by photolysis

Several trifluoromethanesulfonyl(TFMS) derivatives of sugars were prepared and treated with sodium in liquid ammonia or subjected to ultraviolet irradiation. Three 3-$\text{O}$-TFMS derivatives gave the corresponding 3-deoxy compounds, but a 2-$\text{O}$-TFMS derivative gave a branched-chain sugar.     

Cyano-1 ceto-3 et -4 L-rhamnoses

Oxidation of 1-cyano L-rhamnose and 1-cyano 2-deoxy L-arabino 1-hexenopyranose with DMSO-(COCl)₂ or active MnO₂ gives the corresponding 3-ketone, 4-ketone or γ-pyrones.     

Chemical synthesis and isolation of UDP-2-deoxy glucose and galactose

2-Deoxy sugars are attractive compounds in synthetic chemistry with regard to reactivity and stereoselectivity. Moreover, their ability to inhibit enzymes and metabolism is significant in biology. In this study, uridine-5′-diphosphate (UDP)-2-deoxy glucose (11) and galactose (12) were synthesized chemically. These sugar donors for glycosyltransferases were obtained α-selectively via phosphorylation using thioglycosides, coupling reaction with uridine-5′-monophosphate (UMP)-morpholidate, and moderate deacetylation. Isolation was carried out by sequential silica-gel chromatography using two kinds of developing solvents in a refrigerator. The structures were elucidated from the NMR results. Investigation of stability showed that the synthesized UDP-2-deoxy sugars were hydrolyzed much faster in buffer (pH 4) than the natural UDP sugars.     

Self-assembly behavior of phenyl modified β-cyclodextrins

The self-assembly behavior of mono(6-phenolic-6-deoxy)-β-cyclodextrin (1) both in solution and the solid state is comparatively studied by X-ray crystallography and ¹H NMR spectroscopy. The results obtained show that the phenolic groups in the crystal 1 can successively penetrate into the adjacent β-cyclodextrin cavities from the secondary side to form head-to-tail linear polymeric supramolecule with a 2-fold screw axis. The self-assembly behavior also can be determined in D₂O solution, giving a self-association constant of 240 mol⁻¹·L. Using the present and previous structures reported for the relevant β-cyclodextrin derivatives, i.e., mono(6-anilino-6-deoxy)-β-cyclodextrin (2), mono(6-phenylselenyl-6-deoxy)-β-cyclodextrin (3), and mono(6-phenylthio-6-deoxy)-β-cyclodextrin (4), we further reveal the factors governing the formations of supramolecular assemblies.     

Synthèse de sucres aminés ramifiés. IV Synthèse de quelques dérivés nouveaux par l'intermédiaire d'une hexose-spiro-aziridine

Treatment of 3-C-cyano-1,2:5,6-di-O-isopropylidene-3-O-(toluene-p-sulfonyl)-α-D -allofurannose with AlLiH₄ yields a sugar-spiro-aziridine and a branched chain sulfonamide. Reaction mechanisms are briefly discussed and the configurations of the products obtained are proved by chemical reactions. With hydrogenation, the spiro compound is opened to a branched chain amino sugar with the same tertiary carbon as in vancosamine. Several derivatives of this new compound are described: the 6-deoxy sugars in series L and D and the pentose resulting from its oxidation by periodic acid. The conformation around C(4)–C(5) bond is deduced for three compounds from NMR. data.     

Molecular Recognition of Aliphatic Alcohols and Carboxylic Acid by Chromophoric Cyclodextrins

Abstract

Molecular recognition behavior of eight cyclodextrin derivatives, i.e. mono(6-pyridinio-6-deoxy)-α-cyclodextrin (1α), mono(6-pyridinio-6-deoxy)-β-cyclodetrin (1β), mono(6-pyridinio-6-deoxy)-γ-cyclodextrin (1γ), mono[6-(p-picolinio)-6-deoxy]-β-cyclodextrin (2β), mono(6-anilino-6-deoxy)-β-cyclodextrin (3β), mono[6-(m-toluidino)-6-deoxy]-β-cyclodextrin (4β), mono[6-O-(8-quinolyl)]-β-cyclodextrin (5β), and novel mono[6-(2-naphthylamino)-6-deoxy]-β-cyclodextrin (6β), with a series of aliphatic alcohols and carboxylic acid has been investigated spectroscopically. Using the appended aromatic group as a spectral probe, spectroflurometric or spectropolarimetric titrations have been performed at 25°C in aqueous phosphate buffer solution (pH 7.20, 0.1 M) to determine the complex stability constants (K_s ) and Gibbs free energy changes (-δG°) for the stoichiometric 1:1 inclusion complexation of cyclodextrin derivatives with the guests. The results obtained demonstrate that the modified cyclodextrins are highly sensitive to the size/shape and hydrophobicity of guest molecules, and particularly 5β gives an excellent molecular selectivity up to 215 for 1-adamantanol/cyclohexanol. The binding ability and selectivity of the modified cyclodextrins (1α, 1β, and 1β-6β) are discussed from the view points of size/shape-fit concept, induced-fit interaction, and the multiple recognition mechanisms.     

Molecular recognition studies on supramolecular systems (XXIV)

Circular dichroism spectral and fluorescence decay methods have been employed to determine the conformations of mono[6-(p-tolylseleno)-6-deoxy]-β-CD(1), mono(6-anilino-6-deoxy) ?β -CD (2) and mono[6-(L-tryptophan)-6-deoxy]?β -CD (3) in phosphate buffer solution (pH 7.2, 0.1 mol dm^?3) at 298.15 K. The results indicate that compounds 2 and 3 formed self-inclusion complexes in aqueous buffer solution, while the substituent of compound 1 was not included into cyclodextrin cavity at all. Furthermore, the complex stability constant (logK _s) and Gibbs free en-ergy change (?ΔAG °) of these three cylcodextrin derivatives with several cycloalkanols have been determined by circular dichroism spectral titration in phosphate buffer solution at 298.15 K. It is found that the location of the substituent affects the stability of host-guest complex in aqueous solution.     

Synthesis of unnatural 2- and 3-deoxyfuranose analogues

This Letter describes the synthesis of two racemic analogues of unnatural 3′-deoxy and 2′-deoxy sugars, where a phosphorus atom replaces the carbon atom in the 2′- or 3′-position. Two methods of four- and 5-steps were developed affording these new unnatural sugar analogues.     

Conformations and complexation abilities of chemically modified cyclodextrins in aqueous solution

Circular dichroism spectral and fluorescence decay methods have been employed to determine the conformations of mono[6-(p-tolylseleno)-6-deoxy]-β-CD(1), mono(6-anilino-6-deoxy) −β -CD (2) and mono[6-(L-tryptophan)-6-deoxy]−β -CD (3) in phosphate buffer solution (pH 7.2, 0.1 mol dm⁻³) at 298.15 K. The results indicate that compounds 2 and 3 formed self-inclusion complexes in aqueous buffer solution, while the substituent of compound 1 was not included into cyclodextrin cavity at all. Furthermore, the complex stability constant (logK _s) and Gibbs free en-ergy change (−ΔAG °) of these three cylcodextrin derivatives with several cycloalkanols have been determined by circular dichroism spectral titration in phosphate buffer solution at 298.15 K. It is found that the location of the substituent affects the stability of host-guest complex in aqueous solution.     

Elimination Reactions of 2-Deoxy 2-C-Methyl Sugars : Application to the Synthesis of Methyl 2,3,4-Trideoxy-2,4-Di-C-Methyl-6-O-Triphenylmethyl α-D-Lyxo Hexopyranoside and its X Ray Crystal Structure

Abstract

A facile and regiospecific dehydration of 2-deoxy 2-C-methyl sugars using the triphenylphosphine-diethylazodicarboxylate reagent is reported. This reaction allowed us to prepare the title compound which is a crucial intermediate in the total synthesis of natural products. Its absolute configuration is firmly established by X Ray analysis.     

Fluorinated analogs and tritiated enantiomers of inositol (1,3,4)-trisphosphate

The total syntheses of 2-fluoro- and 2,2-difluoro-2-deoxy analogs of DL-myo-Ins (1,3,4)P3 are described. Resolution of a key intermediate followed by borotritide reduction and phosphorylation provided both D- and L-[1-³H]-Ins(1,3,4)P₃ enantiomers with specific activities 15 Ci/mmol.     

Total synthesis of gibberellin A4

A general approach to the preparation of 13-deoxy C₁₉ gibberellins has been established with the total synthesis of (±) gibberellin A₄ ($\text{3}$).     

Rapid Conversion of Unprotected Galactose Analogs to their Udp-Derivatives For Use in the Chemo-Enzymatic Synthesis of Unnatural Oligosaccharides

Abstract

The rapid conversion of D-galactose, its 2-deoxy, 3-deoxy, 4-deoxy and 6-deoxy derivatives and L-arabinose to their UDP-derivatives (2-7) is described. The procedure involves the in situ preparation of the per-O-trimethylsilylated glycopyranosyl iodides and their direct reaction with UDP. All six sugar nucleotides were active as substrates for β(1→4)-galactosyltransferase and were used to enzymatically prepare N-acetyllactosamine (8) and five of its analogs (9-13).     

Culcitosides C2 and C3 from the starfishCulcita novaeguineae

Two steroid glycosides not previously described have been isolated from the digestive system of the starfishCulcite novaeguiniae, and these have been called culcitosides C₂ and C₃. With the aid of chemical and spectral methods, the chemical structure of C₂ has been established as 24ξ-methyl-5α-cholestane-3β,4β,6α,8,15β,16β,28-heptaol 28-O-[O-(2,4-di-O-methyl-β-D-xylopyranosyl)-(1 → 2)-α-L-arabinofuranoside, and that of C₃ as its 4-deoxy analogue.     

Diastereoselective synthesis of branched 2-deoxy sugars via radical c-c bond formation reactions

From glycals 1 and 6, 2-deoxy sugars can be synthesized in 40–72% yields. With 1,2-disubstituted alkenes 3 this radical C-C bond formation reaction leads with high stereoselectivity to the isomers 4 and 8.     

Improved synthesis of 6-amino-6-deoxy-d-galactono-1,6-lactam and d-mannono-1,6-lactam from corresponding unprotected d-hexono-1,4-lactones

Regioselective bromination of unprotected d-galactono-1,4-lactone and d-mannono-1,4-lactone with PPh₃/CBr₄ led to 6-bromo-6-deoxy derivatives. These intermediates were treated with LiN₃ and hydrogenated to give 6-amino-6-deoxy-d-galactono-1,6-lactam (8) and 6-amino-6-deoxy-d-mannono-1,6-lactam (13) in 74 and 67% overall yield, respectively.     

Purine nucleosides XXVIII. The synthesis of 7-(2′-deoxy-α- and β-d-ribofuranosyl)purines from 2′-deoxyribofuranosylimidazoles. Preparation of the 2′-deoxy derivative of the nucleoside from pseudovitamin B12 factor G

The synthesis of 1-(2′-deoxyribofuranosyl)imidazoles have been achieved for the first time via the fusion method of glycosidation. 4-Amino-5-carboxamido-1-(2′-deoxy-α-D-ribofuranosyl)-imidazole ( 8 ) and 4-amino-5-carboxamido-1-(2′-deoxy-β-D-ribofuranosyl)imidazole ( 10 ) have been obtained and their structures established by spectroscopic methods. The first examples of 7-(2′-deoxyglycosyl)purines [7-(2′-deoxy-α-D-ribofuranosyl)hypoxanthine ( 6 ) and 7-(2′-deoxy-β-D-ribofuranosyl)hypoxanthine ( 11 )] have been obtained from the requisite 2′-deoxyribofuranosylimidazoles. The preparation of 6 has furnished the 2′-deoxy derivative (α-configuration) of the nucleoside from pseudovitamin B₁₂ Factor G, which constitutes the first 2′-deoxy derivative of any nucleoside isolated from the various naturally occurring pseudovitamin B₁₂ factors.     

Synthesis of certain 1,2,4-triazole nucleoside derivatives

The syntheses of 3-amino-4-methyl-1-(β-D-ribofuranosyl)-1,2,4-triazolin-5-one ( 8a ) and its 2′-deoxy analog 8b as well as 5-amino-2-methyl-1-(β-D-ribofuranosyl)-1,2,4-triazolin-3-one ( 12 ) have been accomplished. Compounds 8a and 8b were synthesized via glycosylation of 3-bromo-5-nitro-1,2,4-triazole which was followed by replacement in three steps of the 3-bromo function to yield 3-nitro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1,2,4-triazolin-5-one ( 4a ) and its 2′-deoxy analog 4b . Compounds 4a and 4b were methylated at N², hydrogenated and deblocked to give 3-amino-4-methyl-1-(β-D-ribofuranosyl)-1,2,4-triazolin-5-one ( 8a ) and the 2′-deoxy analog 8b . Compound 12 was synthesized by glycosylation of 3-amino-1-methyl-1,2,4-triazolin-5(2H)-one ( 10 ). The structures of 8b and 12 were confirmed by single crystal X-ray diffraction analysis.