Methyl Pyranosides Research Articles

Synthesis of Methoxy‐Substituted Exocyclic (E)‐ and (Z)‐Unsaturated Methyl Pyranosides and a Study of Their Reactivity towards Lewis Acids

AbstractThe first synthesis of methoxy‐substituted exocyclic (E)‐ and (Z)‐unsaturated methyl pyranosides is reported involving the syn elimination of a selenoxide derivative as a key step. The rearrangement of these exocyclic enol ethers in the presence of TIBAL and DIBAL‐H is also described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Crystal structure of methyl-3, 4-O-ethylidene-β-L- arabinopyranoside

The acid-catalyzed ethylidenation of several methyl pentopyranosides has been studied and syntheses of many cyclic alkyl orthoacetates from pentopyranosides have been reported. In a study of the scope and limitation of the reduction of sugar epoxides with diborane/sodium borohydride, methyl-4-O-acetyl-2,3-anhydro-β-L-lyxopyranoside was reduced, yielding two products: methyl-2,3-anhydro-β-L-lyxopyranoside and methyl-3,4-O-ethylidene-β-L-arabinopyranoside. The latter product was characterized by X-ray diffraction and its structure indicates that the epoxide was not reduced as expected; rather, the epoxide was opened by the hydroxyl group of the reduced acetyl. Crystals of the title compound are monoclinic, space group P21 with the following cell dimensions: a = 5.818(l) A, b = 10.842(2) A, c =7.251(1) A, β = 91.47(1)°, Z = 2. Complete three-dimensional data (2θmax = 150° for Cu Kα) were collected on a CAD-4 diffractometer by the ω−2θ scan method. The structure was solved by the application of direct methods and refined by full-matrix least-square methods to a final reliability index of 0.04 for the observed 1031 reflections (I ≥ 3σ). The ethylidene ring has a twist conformation with a torsion angle of −42.8° about the C4–O bond. The pyranose ring is in a flattened chair conformation with the C2–C3–C4–C5 torsion angle of 33.5°. Of the acetal bond lengths, the C5–O5 length, (1.423 A) is shorter than the values found in other methyl pyranosides. O2–H is involved in a bifurcated hydrogen bond intramolecularly to O1 and intermolecularly to O4.

A Glycosylation Driven Strategy for the Synthesis of Anomerically Pure Vinyl Sulfone-modified Pent-2-enofuranoses and Hex-2-enopyranoses

Both α- and β-anomers of vinyl sulfone-modified pent-2-enofuranosides have been synthesized for the first time by taking advantage of the formation of α- and β-methyl glycosides in almost equal ratio only from derivatives of d-xylose. The strategy was equally applicable in the synthesis of α- and β-anomers of vinyl sulfone-modified hex-2-enopyranosides where a d-glucose derivative was selected over a d-allose derivative as the starting material because the former almost exclusively produced the required methyl pyranosides.

Synthesis of Heptano Bridged Pyranoside Derivatives

Addition of dichlorocarbene to the glycal (±±)-2 followed by cyclopropyl-allyl rearrangement leads to the chloro-2H-pyran (±±)-4. Oxidation of (±±)-4 and reduction of the obtained hydroxypyranone (±±)-5 gave the methyl pyranoside (±±)-6. The relative configuration of (±±)-6 was established by X-ray structural analysis of the corresponding acetate (±±)-7. The synthesis of the optically active starting materials (+)-2 and (−)-2 is also reported.

Regioselective methylation of methyl glycopyranosides with diazomethane in the presence of transition-metal chlorides and of boric acid

Partial methylation of the methyl pyranosides of a number of pentoses, hexoses, 6-deoxyhexoses, methyl uronates and their methyl ethers with diazomethane in the presence of transition-metal chlorides and boric acid was studied. It was found for methyl glycosides of pentoses and 6-deoxyhexoses that tin(II), antimony(III), and titanium(IV) chlorides as well as boric acid promoted substitution mainly of OH-3, but with cerium(III) and zinc(II) salts mainly substitution of OH-2 was observed. Methylation of methyl β- l-rhamnopyranoside demonstrated higher reactivity of OH-2 in all cases. The methylation of methyl glycosides of hexoses in the presence of tin(II), antimony(III) and cerium(III) chlorides gave mainly 3-methyl ethers. The 3-methyl ethers, which are not involved in further complexation, accumulated up to 50–80% of the reaction mixture (95–100% of monomethyl ether fraction). Convenient preparative syntheses of methyl ethers for a number of sugars are suggested.

Morphological and biochemical characterization of primary culture of rabbit proximal kidney tubule cells grown on collagen-IV coated Millicell-CM.

The aim of this study was to better characterize rabbit proximal kidney tubule cells cultured on collagen IV-coated porous inserts, as compared to the same cells seeded in standard plastic wells. Total protein contents in confluent monolayers on permeable membranes were about twofold higher than those measured in confluent cultures in plastic wells. Microscopy examinations suggested that such a difference was probably due to a higher cell density and to an impressive development of the apical brush-border membrane. Moreover, measurement of unidirectional transport of p-aminohippuric acid and tetraethylammonium bromide confirmed the high polarization level of cultures on porous inserts. Results of methyl(alpha-D-[U-14C]glyco)pyranoside uptake suggested that cell phenotype was probably influenced by culture conditions. Analysis of different markers as a function of time in culture showed decreases of alkaline phosphatase (AP), gamma-glutamyltranspeptidase (GGT), and Na(+)-K(+)-ATPase activities as well as increases in LDH, ATP, and glutathione levels, similar to those formerly reported for cells cultured in standard plastic plates. However, comparative data from 6-d-old monolayers have shown that AP, GGT, Na(+)-K(+)-ATPase, glutathione reductase (GRED), and selenium-dependent glutathione peroxidase (Se-GPX) activities were 2.8-, 2.6-, 1.6-, 1.2-, and 2.1-fold, respectively, better preserved on precoated permeable membranes. On the other hand, this paper reports for the first time in the literature that GRED and SE-GPX, two phase II detoxification enzymes, were well maintained in cultures of rabbit proximal kidney tubule cells. Our results show that culturing rabbit proximal kidney tubule cells on collagen IV-coated porous membranes was accompanied by an improvement of both morphological and biochemical properties of the cells.

Highly Diastereoselective Synthesis of Pederic Acid Derivatives.

A highly diastereoselective synthesis of methyl pederate (2) is described. A critical feature of the successful route is the introduction of the key C(7)-stereocenter at the stage of 4 via an enantioselective, syn-selective aldol reaction of aldehyde 5 and the chiral acyl oxazolidinone 6. Aldehyde 5, in turn, was prepared from the readily available aldol derivative 7 via a chelate-controlled reaction with allyltrimethylsilane. Intermediate 4 was elaborated to 2 via the intermediacy of 7-O-(3,4-dimethoxybenzyl)pederic acid (3), an intermediate in Kishi's syntheses of mycalamides A and B and onnamide A, by way of methyl pyranoside 10 and the fully protected pederic acid derivative 11.

Molecular motions in solid saccharides studied by NMR spectroscopy

Analyses of spin-lattice relaxation time and second moment measurements of the polycrystalline saccharides methyl α-D-mannopyranoside, methyl β-D-arabinopyranoside, methyl β-L-arabinopyranoside and β-D-allose have revealed, apart from methyl group reorientations in the methyl pyranosides, the jump motion of a hydroxyl proton in a hydrogen bond in β-D-allose and trans-gauche reorientations of CH 2OH groups in methyl α-D-mannopyranoside and β-D-allose.

Samarium(II) iodide promoted ring contraction of carbohydrate derivatives: an expeditious synthesis of functionalised cyclopentanes

Aldehydo methyl pyranosides undergo ring contraction induced by treatment with samarium(II) iodide, in the presence of HMPA and tert-butyl alcohol, to give highly functionalised cyclopentanes.

Characterization of sodium-dependent glucose transport in sheep tracheal epithelium

The nonmetabolizable glucose analogue methyl(alpha-D-[U-14C]gluco)pyranoside ([14C]AMG) was used to study sodium-dependent glucose transport in two preparations: 1) discs punched from strips of sheep tracheal epithelium, and 2) freshly enzyme-isolated sheep tracheal epithelial cells. In discs, cellular accumulation of [14C]AMG was saturable and exhibited a Michaelis-Menten constant (Km) for AMG of 0.63 +/- 0.15 mM. Uptake was linear over 30 min and was inhibited maximally by 100 microM phlorizin [inhibition constant (Ki) approximately 20 nM], by replacement of external sodium with choline or by addition of 10 mM D-glucose (Ki = 0.19 +/- 0.02 mM). Accumulative uptake was activated, in a concentration-dependent manner, by external sodium [affinity constant (Ka) approximately 23 mM] with a Hill coefficient of greater than one but was abolished on depolarizing with high external potassium. In the presence of sodium, D-galactose and AMG both inhibited uptake of [14C]AMG, whereas L-glucose, D-fructose, and D-mannose were ineffective. In isolated cells, [14C]AMG accumulated only in the presence of external sodium and uptake was inhibited by the addition of D-glucose (Ki approximately 0.2 mM), D-galactose, and AMG but not by L-glucose or D-xylose. We conclude that sheep tracheal epithelium exhibits sodium-dependent glucose uptake with a very high affinity for phlorizin, which indicates the presence of a novel isoform of the transporter.

Synthesis of N‐Acetylneuraminic Acid Derivatives and Structural Analogues

AbstractThe cis‐selective Wittig reaction of D‐lyxo‐pentodialdose derivative 2 with C4 building block 3 in the presence of NaN(TMS)2 as a base furnished C9 species 4 which was transformed into ring‐opened derivative 7; diastereoselective epoxidation of the CC double bond with MCPBA afforded the required epoxide 8. Regioselective epoxide opening via trichloroacetimino derivative 9 and cleavage of the derived oxazoline 10 led to 5‐trichloroacetylamido‐substituted compound 11 having from C‐4 to C‐9 the functions and stereochemistry found for neuraminic acid. Regioselective oxidation of the 2‐hydroxy group of 1,2,4,6‐tetra‐O‐unprotected 11 with (Bu3Sn)2O/Br2 afforded directly 2‐nonulose derivative 13 which adopts the pyranose form. Compound 13 could be readily transformed into the known methyl 5‐acetylamido‐3,5‐dideoxy‐D‐glycero‐D‐galacto‐2‐nonulopyranoside (19). Regioselective Cbz protection of the 1‐hydroxy group of 13 and then treatment with MeOH/HCl furnished methyl pyranoside 22. Per‐O‐acetylation and subsequent hydrogenation liberated the primary hydroxy group at C‐1, thus providing after oxidation and esterification of the carboxylic acid moiety N‐dichloroacetylneuraminic acid derivative 25. Treatment with Bu3SnH/AIBN afforded O‐acyl protected Neu5Ac derivative 26. The structure of 26 was confirmed by an independent synthesis from Neu5Ac. magnified image

The assignment of benzyl methylene carbon resonances of per- O-benzylated methyl furanosides: Correlation of assigned chemical shifts with furanosyl-ring structure

Benzyl methylene carbon resonances in perbenzylated methyl furanosides have been assigned by using a combination of INADEQUATE and 13C- 1H shift-correlation n.m.r. spectroscopies. We find that one-bond carbon-carbon coupling constants between furanosyl-ring carbon atoms and the shifts of benzyl methylene carbon resonances are related to the relative orientation of substituents on the furanosyl rings. Re-examination of shift data for perbenzylated methyl pyranosides suggests that the same underlying phenomena similarly influence the shielding of pyranosyl-ring carbon atoms and their benzyl methylene carbon substituents.

ChemInform Abstract: Chemistry of Organosilicon Compounds. Part 218. Stereoselective Synthesis of 3‐(D‐Glycopyranosyl)propenes by Use of Allylsilanes.

AbstractReaction of the allylsilanes (II) with the methyl pyranosides or pyranosyl chlorides (I) and (IV) gives stereoselectively the corresponding C‐α‐D‐glycosides (III) and (V).

ChemInform Abstract: Hetero Diels‐Alder Reactions in Carbohydrate Chemistry: A New Strategy for Multichiral Arrays Synthesis.

AbstractThe dibenzylidene methyl pyranoside (I) is treated with butyllithium and then coupled with the aldehydes (II), yielding the carbinols (III) as a mixture of isomers.

ChemInform Abstract: Synthesis of Methyl Pyranosides and Furanosides of 3-Deoxy-D-manno-oct- 2-ulosonic Acid (KDO) by Acid-Catalysed Solvolysis of the Acetylated Derivatives.

Chemischer InformationsdienstVolume 17, Issue 28 Natural Products ChemInform Abstract: Synthesis of Methyl Pyranosides and Furanosides of 3-Deoxy-D-manno-oct- 2-ulosonic Acid (KDO) by Acid-Catalysed Solvolysis of the Acetylated Derivatives. P. A. MCNICHOLAS, P. A. MCNICHOLASSearch for more papers by this authorM. BATLEY, M. BATLEYSearch for more papers by this authorJ. W. REDMOND, J. W. REDMONDSearch for more papers by this author P. A. MCNICHOLAS, P. A. MCNICHOLASSearch for more papers by this authorM. BATLEY, M. BATLEYSearch for more papers by this authorJ. W. REDMOND, J. W. REDMONDSearch for more papers by this author First published: July 15, 1986 https://doi.org/10.1002/chin.198628327AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume17, Issue28July 15, 1986 RelatedInformation

Synthesis of methyl pyranosides and furanosides of 3-deoxy- d- manno-oct-2-ulosonic acid (KDO) by acid-catalysed solvolysis of the acetylated derivatives

Treatment of methyl 2,4,5,7,8-penta- O-acetyl-3-deoxy-α- d- manno-oct-2-ulopyranosonic acid, or its methyl ester, with refluxing methanolic 0.1 m hydrogen chloride for 16 h gave 95% of methyl (methyl 3-deoxy-α- d- manno-oct-2-ulopyranosid)onate. Acetylation of the methyl ester of 3-deoxy- d- manno-oct-2-ulosonic acid (KDO) gave mainly methyl 2,4,6,7,8-penta- O-acetyl-3-deoxy-α,β- d- manno-oct-2-ulofuranosonate. Treatment of this mixture with methanolic 0.02 m hydrogen chloride at room temperature gave methyl (methyl 3-deoxy-α,β- d- manno-oct-2-ulofuranosid)onate and the corresponding 4-acetates which were isolated by reverse-phase column chromatography of their 7,8- O-isopropylidene derivatives. Confirmation of the position of the isopropylidene group was obtained by acetylation to give methyl (methyl 4,6-di- O-acetyl-3-deoxy-7,8- O-isopropylidene-α,β- d- manno-oct-2-ulofuranosid)onate. The furanose anomers were differentiated primarily by J 3,4 values (α ∼6.1 Hz, β ∼2.2 Hz). The anomeric configuration in the furanose series has been assigned on the basis of optical rotation.

A chiral nitronate dianion from (=d)-glyceraldehyde. Enantiospecific syntheses of 2,3-dideoxy-3-nitro furanosides and pyranosides

A new enantiospecific protocol for the synthesis of 2,3-dideoxy-3- nitro and 3-amino sugars is reported. Chiral nitronate dianion 3, derived from (+)-(=d)-glyceraldehyde, is allylated and the resulting adduct 7 is transformed to either the methyl furanoside 9 or the methyl pyranoside 10 depending on the reaction sequence.

Transposition de l'atome d'azote de dialkylaminopentopyranosides; mise en evidence de sels d'aziridinium intermediaires

Methyl pyranosides with dimethylamino and sulfonyloxy groups in trans relationship undergo rearrangement with participation of the dimethylamino group. This rearrangement results in a 1,2-shift of the nitrogen function which is assumed to be concerted in apolar solvents such as benzene. On the contrary, in water the shift proceeds via an aziridinium ion (observed by NMR) which is opened in a second step, with water or nucleophiles in good yields. The opening of the aziridinium ion has the same regioselectivity as that of corresponding epoxides.

Transport of glucose analogues in rat lung

Uptake of nonmetabolizable glucose analogues was investigated in isolated rat lungs ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate medium. In some experiments, [5-3H]glucose, methyl(alpha-D-[U-14C]gluco)pyranoside (alpha-MG), 3-O-methyl-D-[U-14C]glucose (3-O-MG), or various inhibitors were added to the initial perfusate to determine glucose utilization by the rate of 3H2O production or to characterize the uptake of glucose analogues. [1,2-3H]polyethylene glycol (PEG) was used as an indicator of the extracellular water space and gave a mean value of 0.35 ml/g tissue; calculated mean intracellular H2O space was 0.48 ml/g tissue. Glucose utilization was 56.4 +/- 6.6 (mean +/- SE, n = 6) mumol . g dry wt-1 . h-1 and decreased by 61% with 3 mM phlorizin. After 1-2 h perfusion, intracellular alpha-MG concentration was 1.4-1.9 times the extracellular concentration. The mean tissue-to-medium ratio (T/M) for alpha-MG decreased by more than 30% in the presence of glucose (5.0 mM), phlorizin (0.5 mM), ouabain (0.5 mM), or the absence of external Na+. Intracellular 3-O-MG concentration did not exceed extracellular concentration during 2 h of perfusion and the mean T/M did not change with any of the inhibitors studied. The results indicate that the nonmetabolizable glucose analogue alpha-MG is accumulated against a concentration gradient by an active Na+-dependent transport process, whereas 3-O-MG is apparently taken up by a different mechanism.

The application of molecular mechanics to the structures of carbohydrates

AbstractA study is reported of the accuracy with which the geometries of pyranose and methyl pyranoside molecules are predicted by molecular mechanics. Calculations of the conformational energies of the model compounds dihydroxymethane, methoxymethanol, and dimethoxymethane, made with the program MMI, produced results that compare well with previous ab initio molecular orbital calculations. This indicates that MMI gives a satisfactory account of the energetic and conformational aspects of the anomeric effect, a conclusion further supported by calculations on 2‐methoxytetrahydropyran. The prediction of the observed preferred conformations of the primary alcohol group in aldohexopyranoses appears to be less satisfactory. MMI‐CARB, a version of MMI with changes in some of the equilibrium CO bond lengths of the program, has been used to calculate the geometries of 13 pyranose and methyl pyranoside molecules, the crystal structures of which have been studied by neutron diffraction. When the CCOH torsion angles are constrained to approximately the values observed in the crystal structures, good agreement is obtained between the theoretical and experimental molecular geometries. The rms deviation for CC and CO bonds, excluding those significantly affected by thermal motion in the crystal structure determinations, is 0.005 Å. Corresponding figures for the valence angles that do not involve hydrogen atoms and for the ring torsion angles are 1.2° and 2.0°, respectively. The Cremer and Pople puckering parameters for the pyranose rings are reproduced within 0.026 Å in Q and 5.4° in θ.