Direct anomeric O-arylation and O-hetarylation of glucose - electron deficient aromatic and hetaromatic compounds in aryl and hetaryl glycoside synthesis

Anomeric O-arylation and O-hctarylation of tetra-O-bcnzyl-, tctra-O-acctyl-, and O-unprotected glucose (1a-c) can be directly performed with electron dcficienl aromatic and hctcroaromatic systems having fluoro- (2A-2F) or phenylsulfonyl (3B, 3G-3K), respectively, as leaving groups. The reactions were carried out in DMF as solvent at room temperature with NaH as the base; they led in the products 4 to an exchange of the leaving group by the glucopyranosyloxy moicly; mainly β-products were obtained.     

Selective removal of anomeric O-acetate groups in carbohydrates using HClO4-SiO2

A convenient methodology has been developed for the selective removal of the anomeric acyl group of carbohydrate derivatives using HClO₄-SiO₂ under acidic reaction conditions. Anomeric benzoyl groups can also be removed selectively following similar reaction conditions. The yields were excellent in all cases.     

2-trimethylsilylethyl glycosides. Anomeric deblocking of mono- and disaccharides.

Anomeric deblocking of acetylated, benzylated and unprotected 2-trimethylsilylethyl (TMS-ethyl) glycosides was effected by treatment with trifluoroacetic acid/dichloromethane at 0–25°C for 10–30 min. The yield of deblocked and purified mono- and disaccharides varied between 90 and 95%.     

Anomeric DNA Strand Displacement with α-D Oligonucleotides as Invaders and Ethidium Bromide as Fluorescence Sensor for Duplexes with α/β-, β/β- and α/α-D Configuration

DNA strand displacement is a technique to exchange one strand of a double stranded DNA by another strand (invader). It is an isothermal, enzyme free method driven by single stranded overhangs (toeholds) and is employed in DNA amplification, mismatch detection and nanotechnology. We discovered that anomeric (α/β) DNA can be used for heterochiral strand displacement. Homochiral DNA in β-D configuration was transformed to heterochiral DNA in α-D/β-D configuration and further to homochiral DNA with both strands in α-D configuration. Single stranded α-D DNA acts as invader. Herein, new anomeric displacement systems with and without toeholds were designed. Due to their resistance against enzymatic degradation, the systems are applicable to living cells. The light-up intercalator ethidium bromide is used as fluorescence sensor to follow the progress of displacement. Anomeric DNA displacement shows benefits over canonical DNA in view of toehold free displacement and simple detection by ethidium bromide.     

Development of transition state analogue inhibitors for <Emphasis Type="Italic">N</Emphasis>-acetylglycosyltransferases bearing <Emphasis Type="SmallCaps">d</Emphasis>psico- or <Emphasis Type="SmallCaps">d</Emphasis>tagatofuranose scaffolds

New potential transition state analogue inhibitors for N-acetylglucosyltransferases (GnTs) were synthesised. These compounds based on psico- and tagatofuranose (structure) scaffold contained a 2-thiophenyl-1-O-diethylphosphate moiety mimicking the proposed model of the transition state of the enzymatic reaction catalysed by N-acetylglucosyltransferases. The synthesised compounds as well as their precursors were fully characterised by NMR, optical rotation and mass techniques. Anomeric configuration of tagatofuranose derivatives was confirmed by X-ray crystallography. Two types of potential human glycosyltransferase (GnTs) inhibitors representing donor UDP-GlcNAc, assigned for biological assays on human GnTs, were prepared.     

Analysis of a series of isomeric oligosaccharides by energy‐resolved mass spectrometry: a challenge on homobranched trisaccharides

Glycans exist as part of glycoproteins and glycolipids, which are involved in a variety of biological functions. The analysis of glycan structures, particularly that of structural isomers, is fundamentally important since isomeric glycans often show distinct functions; however, a method for their structural elucidation has not yet been established. Anomeric configurations, linkage positions and branching are the major factors in glycans and their alteration results in a large diversity of glycan structures. The analysis of vicinally substituted oligosaccharides is extremely difficult because the product ions formed in tandem mass spectrometry (MS/MS) often have the same m/z values. In our endeavor to address the issue, we analyzed a series of homo‐substituted trisaccharides consisting only of glucose by collision‐induced dissociation (CID), especially energy‐resolved mass spectrometry (ERMS). It was found that these structurally related glycans could be distinguished by taking advantage of differences in their activation energies in ERMS. Copyright © 2009 John Wiley & Sons, Ltd.     

Enantioselective epoxidation of electrophilic olefins by using glycosyl hydroperoxides

Anomeric hydroperoxides derived from 3,4,6-tri-O-benzyl-galactose and glucose were used for enantioselective epoxidation of naphthoquinone (12), chalcone (13), (E)-1,2-dibenzoyl ethylene (14) and (E)-iso-butyryl-phenyl ethylene (15). In the presence of sodium hydroxide, the epoxidations showed exceptional high asymmetric induction. The exchange of sodium by a potassium ion resulted in a low asymmetric induction. These results pointed to the crucial role of the counterion and strongly suggested that coordination of the alkaline ion occurs in the transition state of the epoxidation process by both reagents, hydroperoxide and the olefin. Theoretical studies of the reaction mechanism at the DFT B3LYP/6-31G* level fitted very well with experimental results.     

Synthesis of 8-Aza-1,3-dideaza-2′-deoxyadenosine and 5,6-Disubstituted Benzotriazole 2′-Deoxy-β-D-Ribofuranosides via Nucleobase-Anion Glycosylation

The synthesis of 8-aza-1,3-dideaza-2′-deoxyadenosine ( 3a ) as well as of 4- and 5,6-substituted benzotriazole 2′-deoxy-β-D -ribonucleosides is described (Schemes 1–3). Glycosylation of benzotriazole anions is stereoselective in all cases (exclusive β-D -anomer formation), but regioisomeric N¹, N², and N³-(2′-deoxyribofuranosides) are formed. The distribution of the regioisomers is controlled by the nucleobase substituents. Anomeric configuration as well as the position of glycosylation are determined by UV and NMR in combination with 1D-NOE-difference spectroscopy. The unprotonated forms of 4-aminobenzotriazoic 2′-deoxy-β-D -ribofuranosides 3a – c exhibit strong fluorescence.     

Phase Transfer Catalyzed Anomeric Nucleophilic Substitutions with D-Xylopyranosyl Halides

Abstract

Anomeric pairs of per-O-acetylated-D-xylopyranosyl halides were individually treated with a wide variety of nucleophiles under mild PTC conditions. Thus, 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide 1 provided exclusively the β-D-xylopyranosyl anomers 2-11 in good to excellent yields (65-95%). Alternatively, under the same PTC conditions, 2,3,4-tri-O-acetyl-β-D-xylopyranosyl chloride 13 afforded solely the inverted α-D-anomers 15 (82%) and 16 (67%) upon treatment with thiophenol and sodium azide, respectively. Similarly, 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl chloride 19 provided the analogous products 20 (63%) and 21 (31%) upon treatment with thiophenol and sodium azide. In the presence of tetrabutylammonium chloride as PTC catalyst, β-xylopyranosyl chloride 13 was shown to slowly equilibrate to the α-chloride 14. Therefore, care must be taken to avoid PTC catalyst for which counter anions can cause anomerization of the starting glycosyl halides.     

Effect of Protecting Groups and Solvents in Anomeric O-Alkylation of Mannopyranose1

Abstract

Anomeric O-alkylation of mannopyranoses with various protecting groups was investigated using mannose derivatives and 2,3-O-isopropylidene-l-O-trifluoro-methanesulfonyl-D-glycerol (1) as alkylating agent. Generally, in polar solvents higher α/β ratios were obtained than in nonpolar solvents. Sterically demanding protecting groups at the 6-O-position and polar solvents led to higher yields. Reactivity differences were explained by different complex formation. Based on these results mannopyranosyl-α(1-4) glucopyranosides 26 and 27 were synthesized using mannose derivatives 5 and 6 having a 6-O-(p-methoxyphenyl)diphenylmethyl group and galactosyl trifluoromethane-sulfonate 24 or nonafluorobutanesulfonate (nonaflate) 25, respectively, as alkylating agents.     

Anomeric DNA: Functionalization of α-d Anomers of 7-Deaza-2′-deoxyadenosine and 2′-Deoxyuridine with Clickable Side Chains and Click Adducts in Homochiral and Heterochiral Double Helices

Anomeric base pairs in heterochiral DNA with strands in the α-d and β-d configurations and homochiral DNA with both strands in α-d configuration were functionalized. The α-d anomers of 2′-deoxyuridine and 7-deaza-2′-deoxyadenosine were synthesized and functionalized with clickable octadiynyl side chains. Nucleosides were protected and converted to phosphoramidites. Solid-phase synthesis furnished 12-mer oligonucleotides, which were hybridized. Pyrene click adducts display fluorescence, a few of them with excimer emission. T_m values and thermodynamic data revealed the following order of duplex stability α/α-d ≫β/β-d ≥α/β-d . CD spectra disclosed that conformational changes occur during hybridization. Functionalized DNAs were modeled and energy minimized. Clickable side chains and bulky click adducts are well accommodated in the grooves of anomeric DNA. The investigation shows for the first time that anomeric DNAs can be functionalized in the same way as canonical DNA for potential applications in nucleic acid chemistry, chemical biology, and DNA material science.     

Stereoelectronic effects and the problem of the choice of model compounds for organic derivatives of a pentacoordinated silicon atom (taking silatranes as an example)

Anomeric effects at the silicon atom in silatranes XSi(OCH₂CH₂)₃N and model trimethoxysilanes XSi(OMe)₃ (X=H, Me, SiH₃, F, Cl) containing a tetracoordinated silicon atom were studied by the MNDO and AM1 methods. Unlike silatranes, the nature of substituent X pronouncedly affects the type and degree of stereoelectronic effects on the values of X−Si−O−C dihedral angles, X−Si bond lengths, and proton affinities of trimethoxysilanes. The results obtained indicate the necessity of modifying the set of spectral and structural indications of pentacoordination of the anomeric silicon atom established previously and observing the principle of conformational similarity for compared compounds. Bicyclic organosilicon ethers XSi(OCH₂)₃CH were proposed to be used as models of corresponding silatranes. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1061–1065, June, 1999.     

Electronic delocalization contribution to the anomeric effect evaluated by computational methods

This study proposes the determination of the electronic delocalization contribution to the Anomeric Effect (EDCAE, Delta Delta E(deloc), eq 3) as a computational alternative in the evaluation of the excess of the axial preference shown by an electronegative substituent located at alpha position to the annular heteroatom of a heterocyclic compound (anomeric position) in both the presence and the absence of electronic delocalization retaining the same molecular geometry. The determination of the EDCAE is computationally accessible through the application of the natural bond orbital analysis (NBO). This type of analysis allows the comparison of hypothetical molecules lacking electronic delocalization (Lewis molecules, in which the electrons are strictly located in bonds and lone pairs) with the fully delocalized molecules retaining the same geometry and the evaluation of the anomeric effect in terms of eq 3. The role of the Lewis molecules is the same as the cyclohexane used experimentally to evaluate the anomeric effect. The advantage of doing this is that Lewis molecules are stereoelectronically inert. Applying this methology to cyclic and acyclic molecules at B3LYP/6-31G(d,p) and HF/6-31G(d,p)//B3LYP/6-31G(d,p) levels of theory, we found that the anomeric effect shown by Cl in 1,3-dioxane; F, Cl, SMe, PH(3), and CO(2)Me groups in 1,3-dithiane is of stereoelectronic nature while the preference of F, OMe, and NH(2) in 1,3-dioxane and the P(O)Me(2) group in 1,3-dithiane is not. Furthermore, this methodology shows that anomeric effects without stereoelectronic origin can modify the molecular geometry in agreement with the geometric pattern required by the double-bond no-bond model, as recently proposed by Perrin.     

Conversion factors for carbohydrate analysis by hydrolysis and <Superscript>1</Superscript>H-NMR spectroscopy

Conversion factor to calibrate the lower xylan content in carbohydrate compositional analysis in wood by ¹H-NMR spectroscopy was investigated. During acid hydrolysis, xylan monomer was dehydrated as furfural, and that furfural was further degraded or condensed in acidic reaction condition. Anomeric hydrogen peaks integration in ¹H-NMR spectroscopic method excluded xylose reacted products (such as furfural and their condensed or degraded products). Only 52% of xylose was counted in anomeric hydrogen integration and 62% of xylose was counted in integration of furfural peak and anomeric hydrogen. For accurate carbohydrate compositional analysis by NMR spectroscopic method, furfural and their reacted products should be counted as xylose. Conversion factor for xylose content analysis was introduced from the acid hydrolysis of several different combinations of standard cellulose and xylan. In this study xylan conversion factor 0.66 was obtained based on compared NMR data from the prepared cellulose and xylan mixtures acid hydrolyzed with the same condition for woodmeal and pulps. With corrected xylan content calculation, NMR spectroscopic method gave rather closer carbohydrate composition compared to the other analytical methods.     

Synthesis of 1-deoxyhept-2-ulosyl-glycono-1,5-lactone utilizing α-selective O-glycosidation of 2,6-anhydro-1-deoxy-d-hept-1-enitols

A series of 1-deoxy-heptulo-2-pyranosyl-glycono-1,5-lactones were synthesized utilizing completely α-selective O-glycosidation of heptenitols. Anomeric configuration of the products was confirmed by ³J_C,H coupling measurement and X-ray crystal structural analysis. The benzyl-protected ketosyl saccharides were partly unstable, and glycosidic linkage was prone to cleave under the usual debenzylation conditions. To prevent this, we surveyed various additives for the Pd-catalyzed hydrogenation reaction and found that basic alumina was the most effective.     

DAIB/TEMPO mediated synthesis of anomeric lactones from anomeric hydroxides

Anomeric sugar lactones are important intermediates for the synthesis of C-glycosides, carbasugars and iminosugars. Herein we present a facile synthesis of anomeric sugar lactones via the DAIB/TEMPO oxidation of anomeric hydroxides. The reactions are very efficient providing the lactones in 2–4 h in almost quantitative yields. The reaction conditions tolerate several common protecting groups used in carbohydrate synthesis. The advantages of the present methodology over previously reported non-metal based methods have also been demonstrated through head to head comparisons. Finally, we have applied the reaction for the sequential conversion of anomeric thioglycosides to the lactones through sequential reactions with NBS followed by the oxidation with DAIB/TEMPO.     

Lanthanum Trifluoromethane-sulfonate‐Catalyzed Facile Synthesis of Per‐O‐acetylated Sugars and Their One‐Pot Conversion to S‐Aryl and O‐Alkyl/Aryl Glycosides†

Lanthanum trifluoromethanesulfonate‐catalyzed solvent‐free per‐O‐acetylation with stoichiometric acetic anhydride proceeds in high yield (95%–99%) to afford exclusively pyranose products as anomeric mixtures. Subsequent anomeric substitution employing borontrifluoride etherate and thiols or alcohols furnished the corresponding 1,2‐trans‐linked thioglycosides and O‐glycosides, respectively, in good to excellent overall yield (75%–85%). Alternatively, reaction of free sugars in neat alcohol employing the same catalyst at elevated temperature gives the corresponding 1,2‐cis‐linked O‐glycosides (along with 1,2‐trans‐linked glycosides as minor product) in good yield (73%–80%). Anomeric mixtures of compounds thus produced were characterized as their per‐O‐acetylated derivatives.      

Deoxy-nitrosugars. 5th Communication. The anomeric effect of the nitro group

The 1-deoxy-1-nitro-D -manno-pyranose 4 was transformed into the nitroolefin 5 and hence into the anomeric 1,2-dideoxy-1-nitro-3, 4, 6-tri-O-benzyl-D -arabino-hexopyranoses ( 3a and 3b ; cf. the Scheme). Conformational analysis of 1-benzyloxy-2-nitroethane ( 6 ) by ¹H-NMR spectroscopy (Fig. 2) showed the synclinal conformation to be more stable than the antiperiplanar one by about 1.4 kcal/mol (attractive gauche-effect). This gauche-effect favours the 1-deoxy-1-nitro-2, 3, 4, 6-tetra-O-benzyl-β-D -manno-hexopyranose ( 1b ) possessing an equatorial nitro group, which is, however, qualitatively the less stable anomer. The relative concentrations of the anomers of 1 and 3 , respectively, were determined by ¹H-NMR spectroscopy after base catalyzed equilibration at 37° in CHCl₃-solution (Table). Anomeric effects for the nitro group of approximately 2.4 kcal/mol in 3 and of approximately 3.4 kcal/mol in 1 were calculated.     

Theoretical and experimental investigation of stereoelectronic interactions in H-complexes of sulfenamide derivatives

The photoelectron and IR spectra of a number of sulfenamide derivatives and their H-complexes have been investigated, A correlation between an increase in the vertical ionization potential of the lone electron pair of the nitrogen atom and a decrease in the frequency shift of the stretching OH-vibrations in the H-complexes of compounds R₃N, R₂NCH₂OR, R₂NSR, and R₂NSOR was found. The electronic and geometric structures of the starting bases and their H-complexes were calculated by theab initio and MNDO methods. Anomeric interactions were found to decrease the energy of the n(N) orbital and to hinder the formation of H-complexes. The calculations of the sulfenamides and their H-complexes in unstable conformations, characterized by increased energies of H-complexation and proton affinity, were also carried out.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2894–2897, December, 1996.     

Stereoelectronic interactions in cyclohexane, 1,3-dioxane, 1, 3-oxathiane, and 1,3-dithiane: W-effect, sigma(C)(-)(X) <--> sigma(C)(-)(H) interactions, anomeric effect-what is really important?

Stereoelectronic effects proposed for C-H bonds in cyclohexane, 1, 3-dioxane, 1,3-oxathiane, and 1,3-dithiane were studied computationally. The balance of three effects, namely, sigma(C)(-)(X) --> sigma(C)(-)(H)()eq, sigma(C)(-)(H)()eq --> sigma(C)(-)(X), and n(p)(X) --> sigma(C)(-)(H)()eq interactions, was necessary to explain the relative elongation of equatorial C(5)-H bonds. The role of homoanomeric n(p) --> sigma(C(5))(-)(H)()eq interaction is especially important in dioxane. In dithiane, distortion of the ring by long C-S bonds dramatically increases overlap of sigma(C(5))(-)(H)()eq and sigma(C)(-)(S) orbitals and energy of the corresponding hyperconjugative interaction. Anomeric n(p)(X) --> sigma(C)(-)(H)()ax interactions with participation of axial C-H bonds dominate at C(2), C(4), and C(6). The balance of hyperconjugative interactions involving C-H(ax) and C-H(eq) bonds agrees well with the relative bond lengths for all C-H(ax)/C-H(eq) pairs in all studied compounds. At the same time, the order of one-bond spin-spin coupling constants does not correlate with the balance of stereoelectronic effects in dithiane and oxathiane displaying genuine reverse Perlin effect.