Xylo Configuration Research Articles

Synthesis of N-glycosyl amides: conformational analysis and evaluation as inhibitors of β-galactosidase from E. coli.

The synthesis of N-glycosyl amides typically involves the use of glycosyl amines as direct precursors, resulting in low yields due to hydrolysis and the loss of stereocontrol through anomerization processes. In this study, a sequential synthesis of N-glycosyl amides is proposed, employing glycosyl amines as intermediates obtained from glycosyl azides. Derivatives with gluco, galacto, or xylo configurations were synthesized. Hexose derivatives were obtained under stereocontrol to give only the β anomer, while the xylo derivatives provided a mixture of α and β anomers. Conformational analysis revealed that all β anomers adopted the 4C1 conformation, while α anomers were found in the 1C4 chair as the major conformer. After de-O-acetylation, the derivatives containing a galactose unit were evaluated as inhibitors of β-galactosidase from E. coli and were found to be moderate inhibitors.

Highly Efficient Inversion of the C-3 Configuration in 1,2-O-Isopropylidenefuranose Derivatives by an Adapted Swern Oxidation/Sodium Borohydride Reduction Protocol in One Pot

One pot Swern oxidation-sodium borohydride reduction of 1,2-O-isopropylidenefuranose derivatives having the D-gluco or D- xylo configurations led to the corresponding stereoisomers resulting from the stereoselective inversion of C-3. This method is a simple adaptation to the traditional procedure that consists in quenching the Swern oxidation at -60 oC with a mixture of H2O/EtOH (1:4), in which NaBH4 is dissolved. Thus, the inversion of the configuration at C-3 of 1,2-O-isopropylidenefuranose derivatives is accomplished in yields up to 98%.

Synthesis of 3'-fluoro-tRNA analogues for exploring non-ribosomal peptide synthesis in bacteria.

Aminoacyl-tRNAs (aa-tRNAs) participate in a vast repertoire of metabolic pathways, including the synthesis of the peptidoglycan network in the cell walls of bacterial pathogens. Synthesis of aminoacyl-tRNA analogues is critical for further understanding the mechanisms of these reactions. Here we report the semi-synthesis of 3'-fluoro analogues of Ala-tRNA(Ala) . The presence of fluorine in the 3'-position blocks Ala at the 2'-position by preventing spontaneous migration of the residue between positions 2' and 3'. NMR analyses showed that substitution of the 3'-hydroxy group by fluorine in the ribo configuration favours the S-type conformation of the furanose ring of terminal adenosine A76. In contrast, the N-type conformation is favoured by the presence of fluorine in the xylo configuration. Thus, introduction of fluorine in the ribo and xylo configurations affects the conformation of the furanose ring in reciprocal ways. These compounds should provide insight into substrate recognition by Fem transferases and the Ala-tRNA synthetases.

Polyurethanes derived from carbohydrates and cystine‐based monomers

ABSTRACTLinear [m,n]‐type polyurethanes (PUs) fully based on renewable materials are synthesized by interfacial polycondensation reaction of diamines derived from the amino‐acid cystine with (bis)chloroformates derived from alditols having L‐arabino or xylo configuration. The degradability of the new PUs has been enhanced by the introduction of disulfide linkages into the polymer backbone leading to a new group of stimulus‐responsive sugar‐based polyurethanes able to be degraded by glutathione under physiological conditions. All these polyurethanes are stable up to around 245°C, decomposing at higher temperatures through a one‐stage mechanism. The new materials display high chemical homogeneity and degradability in both hydrolytic and reductive environments, with reductions of above 90% in Mw. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41304.

β-Mannosidase and β-hexosaminidase inhibitors: synthesis of 1,2-bis- epi-valienamine and 1- epi-2-acetamido-2-deoxy-valienamine from d-mannose

A partially protected C-5 C-5a unsaturated carbasugar with α- lyxo configuration is synthesised in five steps and 26% overall yield from a known mannose-derived hemiacetal, using ring-closing metathesis as a key step. This carbasugar is converted into valienamine derivatives with β- lyxo (i.e., corresponding to β- manno at C-1–C-4), α- lyxo (i.e., corresponding to α- manno at C-1–C-4) and β-2-acetamido-2-deoxy- xylo (i.e., corresponding to β-GlcNAc at C-1–C-4) configurations. This is the first report of the synthesis of the β- lyxo compound, 1,2-bis- epi-valienamine, which was found to inhibit Cellulomonas fimi β-mannosidase (CfMan2A) with K i 140 μM. We report the crystal structures of three protected C-5 C-5a unsaturated carbasugars with lyxo configuration.

Stereoselective cyclopropanation of unsaturated acetals, using carbohydrates with d- gluco, l- rhamno and d- xylo configurations as chiral auxiliaries

The stereoselective synthesis of (2-phenylcyclopropyl)methylidene acetals of sugar derivatives from methyl d-glucopyranoside, dodecyl N-acetyl-2-amino-2-deoxy- d-glucopyranoside, 1,2- O-isopropylidene- d-glucofuranose, methyl l-rhamnopyranoside and 1,2- O-isopropylidene- d-xylofuranose, as a chiral auxiliary, is described. The cyclopropanation reaction of the corresponding alkenylidene derivatives with CH 2I 2/ZnEt 2 took place with different stereoselectivity, depending on the configuration on the acetal carbon, the size of the acetal ring, the sugar configuration, the protecting group of the hydroxyl groups of the sugar and the substitution of the unsaturated system. The stereochemistry of the new stereogenic centres was then determined by acid hydrolysis of the cyclopropane moiety of the chiral auxiliary, which was also recovered.

Comprehensive Structural Studies of 2′,3′-Difluorinated Nucleosides: Comparison of Theory, Solution, and Solid State

The conformations of three 2',3'-difluoro uridine nucleosides were studied by X-ray crystallography, NMR spectroscopy, and ab initio calculations in an attempt to define the roles that the two vicinal fluorine atoms play in the puckering preferences of the furanose ring. Two of the compounds examined contained fluorine atoms in either the arabino or xylo dispositions at C2' and C3' of a 2',3'-dideoxyuridine system. The third compound also incorporated fluorine atoms in the xylo configuration on the furanose ring but was substituted with a 6-azauracil base in place of uracil. A battery of NMR experiments in D 2O solution was used to identify conformational preferences primarily from coupling constant and NOE data. Both (1)H and (19)F NMR data were used to ascertain the preferred sugar pucker of the furanose ring through the use of the program PSEUROT. Compound-dependent parameters used in the PSEUROT calculations were newly derived from complete sets of conformations calculated from high-level ab initio methods. The solution and theoretical data were compared to the conformations of each molecule in the solid state. It was shown that both gauche and antiperiplanar effects may be operative to maintain a pseudodiaxial arrangement of the C2' and C3' vicinal fluorine atoms. These data, along with previously reported data by us and others concerning monofluorinated nucleoside conformations, were used to propose a model of how fluorine influences different aspects of nucleoside conformations.

Two Straightforward Strategies for the Synthesis of Thiodisaccharides with a Furanose Unit as the Nonreducing End

AbstractThiodisaccharides having a 1‐thiopentofuranose nonreducing end were synthesized by two routes starting from per‐O‐acylaldofuranoses with arabino, ribo, and xylo configurations. These glycosyl donors were converted into S‐glycosyl isothiourea derivatives as precursors of 1‐thiofuranose units, which were generated in situ and trapped by a sugar enone to produce, by Michael addition, the thioglycosidic linkage. Alternatively, the MoO2Cl2‐promoted glycosylation of the thiol group of 6‐thiosugar derivatives by per‐O‐acylfuranose led to thiodisaccharides with exclusive 1,2‐trans diastereocontrol.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Stereoselective epoxidation of alkenylidene acetals derived from carbohydrates with d- allo, d- altro, d- galacto, d- gluco and d- xylo configurations

The synthesis of 2,3-epoxypropylidene acetals of sugar derivatives from N-acetyl-2-amino-2-deoxy- d-allopyranose, d-altropyranose, d-galactopyranose, N-acetyl- d-glucosamine, d-glucofuranose and d-xylofuranose is described. The epoxidation with m-CPBA of the corresponding alkenylidene derivatives took place with different stereoselectivities depending upon the sugar configuration, the protecting group of the hydroxyl groups of the sugar, and the substitution of the unsaturated system. The analysis of the ring-opening reaction of these oxiranes by hydrogenolysis enabled the assignation of their configuration at the new stereogenic centres.

Stereoselective Synthesis of 2‐Deoxy‐2‐iodo‐glycosides from Furanoses. A New Route to 2‐Deoxy‐glycosides and 2‐Deoxy‐oligosaccharides of ribo and xylo Configuration.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Stereoselective Synthesis of 2-Deoxy-2-iodo-glycosides from Furanoses. A New Route to 2-Deoxy-glycosides and 2-Deoxy-oligosaccharides of ribo and xylo Configuration

[reaction: see text] A general procedure for the stereoselective synthesis of 2-deoxy-2-iodo-hexo- and -hepto-pyranosyl glycosides from furanoses is reported. The proposed methodology provides a new route for accessing 2-deoxy-oligosaccharides. The procedure involves three reactions: Wittig-Horner olefination to give alkenyl sulfanyl derivatives, electrophilic iodine-induced cyclization to give phenyl 2-deoxy-2-iodo-1-thio-hexo-glycosides, and glycosylation. Protected furanoses 1, 3, and 6-11, which include examples of the four possible isomeric configurations of furanoses, were reacted with diphenyl phenylsulfanylmethyl phosphine oxide to give the alkenyl sulfanyl derivatives 2, 4, and 12-16. The iodine-induced cyclization of these compounds afforded the phenyl 2-deoxy-2-iodo-1-thio-glycosides 18, 20, and 22-27 with practically complete regio- and stereoselectivity. Products of 6-endo cyclization, in which the iodine at C-2 was in a cis relationship with the alkoxy at C-3, were almost exclusively produced. Better yields were obtained for compounds with a ribo or xylo configuration than for compounds with other configurations. Compounds 18, 20, and 22-27 were found to be efficient glycosyl donors in the glycosylation of cholesterol and glucopyranoside 29a, affording the corresponding 2-deoxy-2-iodo-glycosides and 2-deoxy-2-iodo-oligosaccharides with good yields and stereoselectivities. The glycosydic bond in the major isomers was always trans to the iodine at C-2.

Ribo-, Xylo-, and Arabino-Configured Adenine-Based Nucleoside Phosphonates: Synthesis of Monomers for Solid-Phase Oligonucleotide Assembly

Adenine-based, regioisomeric nucleoside phosphonates with ribo, xylo and arabino configuration were synthesized in the protected form suitable for the phosphotriester-like, solid-phase synthesis of oligonucleotides. Phosphonate moiety was protected by 4-methoxy-1-oxido-2-picolyl group and the furanose hydroxyl by the dimethoxytrityl group.

Preparation of 3,5-bis-(β- d -glycopyranosyl)-1,2,4-thiadiazoles from C -(β- d -glycopyranosyl)thioformamides

Abstract Acylated C-glycopyranosyl thioformamides of d -gluco, d -galacto, and d -xylo configuration were obtained by treating the corresponding glycosyl cyanides with hydrogen sulfide in the presence of triethylamine. The thioformamides gave 3,5-bis-(β- d -glycopyranosyl)-1,2,4-thiadiazoles in reactions with potassium bromate and sodium dithionite in dichloromethane–water biphasic solvent mixture. Deprotected derivatives were prepared by Zemplen deacylation.

Lipo-oligosaccharidic antigen from Mycobacterium gastri. Complete structure of a novel C4-branched 3,6-dideoxy-alpha-xylo-hexopyranose.

The following incomplete structure, alpha-X-(1-->3)-[beta-L-Xylp-(1-->4)]6-3-O-Me-alpha-Rhap-(1- ->3)- beta-D-Galp-(1-->3)-beta-D-Glcp-(1-->4)-2-O-acyl-alpha-D-Glcp-(1<-->1)-4 ,6-di-O-acyl-alpha-D-Glcp, was previously established for the antigenic lipo-oligosaccharide typifying Mycobacterium gastri, namely, LOS-III. The partial structure of the distal monosaccharide (X) was assigned as 3,6-dideoxy-4-C-(1,3-di-O-methylpropyl)-alpha-hexopyranose, which corresponds to a new-found monosaccharide in nature [Gilleron M., Vercauteren J., & Puzo G. (1993) J. Biol. Chem. 268, 3168-3179]. This article reports the complete structure of X, which was determined from the FAB-MS and 2D NMR analysis of the peracetylated LOS-III. The comparative analyses of the native and per-O-acetylated LOS-III FAB-MS spectra revealed, for the monosaccharide X, a molecular mass of 370 Da and five hydroxyl groups that could be acetylated. Additionally, the 1D 1H NMR spectrum of the per-O-acetylated LOS-III showed a dramatically increased dispersion of the protons, which resonated between 3 and 4 ppm in the spectrum of the underivatized LOS-III. Thus, thanks to 2D NMR sequences (COSY, HOHAHA, HMQC, HMQC-HOHAHA, and HMBC), the complete assignment of the 1H and 13C signals was achieved. Starting from the quaternary C4 resonance, the spin system of the C-alkyl chain was assigned, allowing us to propose the following structure, 3,6-dideoxy-4-C-(1,3-dimethoxy-4,5,6,7-tetrahydroxyheptyl)-alpha-x ylo- hexopyranose. The xylo configuration was established from the ROESY spectrum.

Addition of N-benzylhydrazine to sugar δ-enlactones

The conjugate addition - rearrangement of N-benzylhydrazine to sugar δ-enlactone with erythro configuration 1 and 2 affords mixtures of respective ribo and arabino isomers with the former one prevailing. In the case of the threo lactone 3 two regioisomers with xylo configuration are produced, whereas in the case of 4 only one isomer with the erythro configuration is formed. The stereochemical course of these rections was explained.

TSAO analogues. 3. Synthesis and anti-HIV-1 activity of 2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl 3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) purine and purine-modified nucleosides.

Several purine and purine-modified analogues of the new lead anti-HIV-1 agent [[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl] thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO-T) have been prepared and evaluated as inhibitors of HIV-1-induced cytopathicity. Reaction of O-mesylcyanohydrins of furanos-3'-ulosyladenine with Cs2CO3 afforded beta-D-xylo- and ribofuranosyladenine 3'-spiro nucleosides. Reaction of 1,2-di-O-acetyl-5-O-benzoyl-3-C-cyano-3-O-mesyl-D-ribofuranose with purine bases, followed by treatment with Cs2CO3, stereoselectively afforded beta-D-ribofuranosyl 3'-spiro nucleosides. 2',5'-O-Deacylation and subsequent treatment with tert-butyldimethylsilyl chloride gave the required TSAO derivatives. The 3'-spiro nucleosides with a xylo configuration did not show any anti-HIV activity. However, the purine ribo 3'-spiro nucleosides were potent and selective inhibitors of HIV-1 with a 50% effective concentration in the range of 0.1-1 microM and a selectivity index ranging from 2 to 3 orders of magnitude. Introduction of an alkyl function at N-1 of the purine moiety markedly decreased cytotoxicity without affecting antiviral activity.

3'-Spiro nucleosides, a new class of specific human immunodeficiency virus type 1 inhibitors: synthesis and antiviral activity of [2'-5'-bis-O-(tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranose]-3'-spiro-5"-[4"-amino-1",2"-oxathiole 2",2"-dioxide] (TSAO) pyrimidine nucleosides.

A series of 3'-spiro nucleosides have been synthesized and evaluated as anti-HIV-1 agents. Reaction of O-mesylcyanohydrins of furanos-3'-ulosyl nucleosides with base afforded [1-[2',5'-bis-O- (tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranosyl]]-3'-spiro-5"- [4"-amino-1",2"-oxathiole 2",2"-dioxide] derivatives of thymine, uracil and 4-N-acetylcytosine 11 and 12. Desilylation of 11 and 12 gave the full deprotected 3'-spiro xylo- and ribofuranosyl nucleosides 13 and 14 or the partially 5'-O-deprotected-3'-spiro beta-D-xylo- and -ribo-nucleosides 15 and 16, or 2'-O-deprotected-3'-spiro beta-D-ribo-nucleoside 17. 2'-Deoxygenation of 17 afforded 2'-deoxy-3'-spiro beta-D-erythro-pentofuranosyl derivative 18. These 3'-spiro derivatives were evaluated for their anti-HIV-1 activity. All 3'-spiro nucleosides having a xylo configuration did not show any anti-HIV-1 activity. 3'-Spiro ribo-nucleosides with none or only one silyl group at C-2' or C-5' or the 2'-deoxy derivative were also inactive at subtoxic concentrations. However, 3'-spiro ribo-nucleosides having two silyl groups at C-2' and C-5' were potent and selective inhibitors of HIV-1. None of the nucleoside analogues that showed anti-HIV-1 activity proved inhibitory to the replication of HIV-2 or SIV.

Synthesis of 3'-Fluoro-3'-Deoxyribonucleosides; Anti-HIV-1 and Cytostatic Properties

Abstract It has generally proven difficult to synthesize ribonucleosides with sugar modifications at the 3′ position. We now present a practical route for the synthesis of ribonucleosides with a 3′ fluorine substituent. Nucleosides with the xylo configuration were prepared by sugar-base condensation. Tritylation of the unprotected nucleosides gave a mixture of 2′,5′ and 3′,5′ bistritylated nucleosides which were difficult to characterize. Therefore the necessary precursors were synthesized in a step-wise fashion, starting with selective deprotection of the 2′-acyl group, followed by tritylation. This gave the 2′,5′-tritylated xylonucleosides in good yield. Reaction with diethylaminosulfur trifluoride and deprotection with 80 % acetic acid provided the 3′-fluoro-3′-deoxyribonucleosides 1, 2 and 4. The cytidine derivative was synthesized from 1 by reaction with trifluoromethanesulfonic anhydride followed by ammonia. Treatment of 4 with adenosine deaminase yielded 5.

Stereoselective syntheses of alcohols, XXVI. Synthesis of 3‐methyl‐2,6‐dideoxyhexoses by addition of an allenyltitanium reagent to aldehydes

AbstractIn contrast to the nonregioselective addition of 3‐methoxy‐3‐methylallenyllithium (8) to aldehydes the corresponding titanium reagent 14 produced only propargylic type adducts. The products resulting on addition of 14 to L‐2‐(benzyloxy)propionaldehyde have been converted into 3‐O‐methyl‐3‐methyl‐2,6‐dideoxyhexoses 23 and 25 of arabino and xylo configuration.

Synthesis and hydrogenation studies of 3-azidohex-2-enopyranosides, precursors of the sugar constituents of anthracycline glycosides

Application of the allylic azide rearrangement/ N-iodosuccinimide glycosylation procedure to 3,4-di- O-acetyl- l-fucal gave exclusively benzyl 4- O-acetyl-3-azido-2,3,6-trideoxy-2-iodo-α- l-idopyranoside. A similar reaction of 3,4-di- O-acetyl- l-rhamnal gave both the corresponding l- altro ( 12) and l- manno glycosides ( 14) in the ratio 4:1. Deacetylation of 12 and 14 and oxidation of the products with pyridinium dichromate also caused the elimination of hydrogen iodide and gave crystalline benzyl 3-azido-2,3,6-trideoxy-α- l- glycero-hex-2-enopyranosid-4-ulose ( 18). Reduction of 18 with sodium borohydride at low temperature gave benzyl 3-azido-2,3,6-trideoxy-α- l- erythro-hex-2-enopyranoside ( 19). The crystalline mesylate of 19 was treated with caesium propionate, and the product 22 was saponified to give benzyl 3-azido-2,3,6-trideoxy-α- l- threo-hex-2-enopyranoside, a suitable A unit precursor for the sequential synthesis of class II anthracycline oligosaccharides. The stereospecific formation of the 3-acetamido-2,3,6-trideoxy-α- l-glycosides with the ribo or xylo configurations could be achieved by reduction of 19 and 22, respectively, with sodium borohydride.