Novel Disaccharides Containing 3-Deoxy-D-Manno-2-Octulosonic Acid (KDO) and Lipid a Subunit Analogs

Abstract

3-Deoxy-D-manno-2-octulosonic acid (KDO)₁ is a prominent constituent of bacterial lipopolysaccharides (LPS),₂ and recently it has been demonstrated _3,4 that the KDO part in the core region of LPS is α-ketosidically linked to 0-6′ of the o-glucosamine-disaccharide backbone of lipid A. Although the portion, including KDO, has been suggested_5,6 to be necessary for expression of antitumor and interleukin 1 (IL 1)-induction activities of LPS, the disticnt biological roles of KDO in LPS are still obscure.     

Structural studies on Helicobacter pylori 3‐deoxy‐D‐manno‐2‐octulosonate‐8‐phosphate synthase using electrospray ionization mass spectrometry: a tetrameric complex composed of dimeric dimers

Helicobacter pylori 3‐deoxy‐D ‐manno‐2‐octulosonate‐8‐phosphate (KDO8P) synthase catalyzes the conversion of D ‐arabinose‐5‐phosphate (A5P) and phosphoenolpyruvate (PEP) to produce KDO8P and inorganic phosphate. Since this protein is absent in mammals, it might therefore be an attractive target for the development of new antibiotics. Unlike E. coli KDO8P synthase (class I), the H. pylori counterpart is a class II enzyme, where it requires a divalent transition metal ion for catalysis. Although the metal ions have been shown to be important for catalysis, their role in the structure is not understood. Using electrospray ionization mass spectrometry (ESI‐MS), the role of the metal ions in H. pylori KDO8P synthase has been investigated. This protein is found to be a tetramer in the gas phase but dissociates into the dimer with increasing declustering potential (DP2) suggesting an existence of a ‘structurally specific’ tetramer. An examination of mass spectra revealed that the tetrameric state of the Cd²⁺‐reconstituted enzyme is less stable than those of the Zn²⁺‐, Co²⁺‐ and Cu²⁺‐enzymes. The stoichiometry of metal binding to the protein depends on the nature of the metal ion. Taken together, our data suggest that divalent metal ions play an important role in the quaternary structure of the protein and the tetrameric state may be primarily responsible for catalysis. This study demonstrates the first structural characterization and stoichiometry of metal binding in class II KDO8P synthase using electrospray ionization quadrupole time‐of‐flight mass spectrometry under nondenaturing conditions. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis of the Core Oligosaccharides of Lipooligosaccharides from Campylobacter jejuni: A Putative Cause of Guillain–Barré Syndrome

The chemical synthesis of the highly branched core oligosaccharides of lipooligosaccharides (LOSs) found in Campylobacter jejuni, which causes Guillain–Barré syndrome by a preceding infection, is described. The target LOS mimics, consisting of eight or nine monosaccharides, were classified into three groups as key building blocks: ganglioside-core tetra-/pentasaccharides (GM1-/GD1a-like), l -glycero-d -manno-heptose-containing trisaccharides, and 3-deoxy-d -manno-2-octulosonic acid (KDO) residues. These synthetic fragments were obtained from commercially available monosaccharides. Less obtainable l -glycero-d -manno-heptose and KDO residues, as key components of the LOSs, were synthesized from p-methoxyphenyl d -mannoside and di-O-isopropylidene-protected d -mannose, respectively. The synthesis of α-KDO glycoside, as one of the most difficult stereocontrolled glycosidic constructions, was achieved by treating a 2,3-ene derivative of KDO with phenylselenyl trifluoromethanesulfonate as a suitable α-directing reagent. All synthetic blocks were constructed through a convergent synthetic route, which resulted in the first synthesis of structurally challenging LOS core glycans containing ganglioside GM1 and GD1a-core sequences.     

Homoallylic Phosphonates: Useful Precursors for 3,4-Epoxyalkanephosphonates

Abstract

Exoxyalkanephosphonates are compounds of interest as potential drugs¹ or intermediates in various synthetic transformations^2. Especially 1,2-epoxyalkanephosphonates and 2,3-epoxyalkanephos-phonates attracted much attention and many preparatively useful routes to these compounds have been reported^3. On the other hand the synthesis of 3,4-epoxyalkanephosphonates has to our knowledge not been described?.     

Detection of Al3+ and Hg2+ ions with anthracene appended Schiff base and its reduced analogue

Abstract

Chemosensor 1 has been synthesized via a one-pot synthetic route incorporating anthracene and azomethine (HC═N—) units acting as signaling and binding units, respectively. Chemosensor 1 offered selective colorimetric and fluorometric response towards Al³⁺ and Hg²⁺ ions among other cations in CH₃OH. Solution of 1 in methanol exhibited a naked eye color transition from yellow to colorless on addition of Al³⁺ and Hg²⁺ ions. In case of emission experiments, non-fluorescent solution of 1 showed major enhancement in intensity giving blue fluorescence for both metal ions. The limits of detection were calculated to be 1.04 and 0.8 µM for Al³⁺ and Hg²⁺, respectively, using fluorescence titrations. Further, reduced form of Schiff base 1 (2) has also been synthesized in order to compare the importance of azomethine (HC═N—) and (H₂C—NH—) moieties in selective coordination. However, the reduced analogue 2 did not exhibit selective detection towards any of the ions.     

Observation of a chemically labile,noncovalent enzyme intermediate in the reaction of metal‐dependent Aquifex pyrophilus KDO8PS by time‐resolved mass spectrometry

The direct detection of intermediates in enzymatic reactions can yield important mechanistic insights but may be difficult due to short intermediate lifetimes and chemical instability. Using a rapid‐mixing device coupled with electrospray ionization time‐of‐flight mass spectrometry, the noncovalent hemiketal intermediate in the reaction of metal‐dependent 3‐deoxy‐D‐manno‐octulosonate‐8‐phosphate (KDO8P) synthase from Aquifex pyrophilus was observed in the millisecond time range. Using single turnover conditions, the noncovalent complexes of enzyme with Cd²⁺:phosphoenolpyruvate, Cd²⁺:phosphate, Cd²⁺:KDO8P, and Cd²⁺:intermediate complexes were resolved. The intermediate complex is present during times ranging from 50–630 ms, indicating that the intermediate builds up at the ambient temperatures of the experiment. This represents the first direct detection of the intermediate with a native metal‐dependent KDO8PS, and further demonstrates that time‐resolved mass spectrometry is a useful tool in mechanistic studies of enzymatic reactions. Copyright © 2010 John Wiley & Sons, Ltd.     

A New Spectrophotometric Method for the Determination of Maneb in Commercial Formulations

Abstract

A new rapid, selective and sensitive method has been developed for the determination of maneb using pyrocatechol-violet(PV) as chelating reagent in the pH range of 7.5–11.0 in the presence of CTAB producing a complex which shows maximum absorption at 640 nm. Working range of the method is 0.2–3.0 μg ml^?1 maneb (manganese ethylenebisdithiocarbamate). The molar absorptivity of the color system is 79600 1 mol^?1 cm^?1 and Sandell's sensitivity is 0.0033 μg cm^?2. The reproducibility of the method has been checked by the 10 replicate analysis of 15 μg of maneb in 10 ml of solution. The method is quite sensitive and has been applied for the determination of maneb in various commercial samples, crops, grains and synthetic samples.     

Mn(III) Hexafluoroacetylacetonate as an Oxidative Agent in the Synthesis of Heterobimetallic <Emphasis Type="Italic">β</Emphasis>-Diketonates

New synthetic approach for the preparation of heterometallic β-diketonates has been developed. Three manganese-containing diketonates, InMn(hfac)₃ (1), CdMn₂(hfac)₆ (2), and Hg₂Mn₂(hfac)₆ (3), have been isolated in quantitative yields by employing the solid state redox reaction of Mn(hfac)₃ with transition and main group metals. The heterometallic molecules are built on Lewis acid–base interactions between diketonate oxygens of the [Mn(hfac)₃]⁻ groups and “naked” metal centers that appear in the form of In⁺, Cd²⁺, and Hg₂²⁺ cations. Compounds 1–3 have been shown to retain a heterometallic structure upon sublimation–deposition procedure as well as in solutions of non-coordinating solvents.     

Ring–Opening of a Carbohydrate Triflate to form an Acyclic Alkene

ABSTRACT

The ease with which carbohydrate trifluoromethanesulfonates (triflates) undergo substitution reactions with a wide variety of nucleophiles¹ has allowed these compounds to play an increasingly important role in synthetic carbohydrate chemistry.² The exceptional reactivity of triflates also creates an opportunity for unusual reactions to occur;³ for example, triflyl group migration⁴ and internal displacement by very weak nucleophiles⁵ both have been observed. Also, carbohydrate triflates have been used as alkylating agents in oligosaccharide synthesis.⁶ In this communication a new triflate reaction is described. This new process is one in which departure of the triflyloxy group is accompanied by ring opening to give an acyclic alkene.     

Bis(naphthol)-based fluorescent chemoprobe for cesium cation and its immobilisation on silica nanoparticle as a high selective adsorbent

Abstract

A bis(naphthol)-based cation receptor 1 has been synthesised by three steps of synthetic procedure. The spectroscopic properties of 1 upon addition of various metal ions were investigated by UV–vis absorption and fluorescence spectroscopy. As a result, the absorption of 1 was linearly decreased as a function of concentration of added Cs⁺. Also, 1 exhibited dramatic fluorescence quenching effect upon exposure to caesium cation. Contrastively, no significant quenching effect was observed upon addition of other metal ions such as Na⁺, K⁺, Rb⁺, Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺, Ni²⁺ and Zn²⁺. It was found that 1 formed a 1:1 complex with Cs⁺ by Job’s plot. Furthermore, we also prepared 1-functionalised silica nanoparticle (SiO₂-1) as an adsorbent for Cs⁺. SiO₂-1 showed a great capacity for selective removal of caesium ion from aqueous solution as well as from tap water. Thus, it is potentially useful for the detection and removal of caesium cation from environmental and biological fluids polluted by nuclear radiation and nuclear waste.     

Selenium-Containing π-Conjugated Compounds for Electronic Molecular Materials

Abstract

Novel selenium-containing π-conjugated compounds have been studied for the development of organic metals, superconductors, and field-effect-transistors. Methylenedithiotetraselenafulvalene (MDT-TSF) and its related electron donors are effectively synthesized by the recently developed synthetic method consisting of the one-pot formation of 1,3-diselenole-2-selones, the deprotection/realkylation procedure of the protected tetrachalcogenafulvalene-thiolate and -selenolate, and the ring closing reaction via trans-alkylation on sulfur or selenium atom. These new compounds serve as good electron donors for developing not only highly conducting charge-transfer salts (> 10 ³ S cm^?1) but also superconducting salts. Among six selenium-containing methylenedichalcogeno-tetrachalcogenafulvalenes, we found that four of them can produce superconducting salts, indicating that the present compounds are superior class of electron donors.

For the development of high-performance organic semiconductors for organic field effect transistor (OFET) devices, we focused our attention to selenophene-containing acene-type compounds, namely benzo[1,2-b:4,5-b′]diselenophene (BDS) derivatives hitherto unknown. A new synthetic method for BDS derivatives consisting of double heterocycle-formation on the central benzene ring has been established and has made it possible to synthesize a range of BDS derivatives. Among them, 2,6-diphenyl derivative (DPh-BDS) shows very high hole mobility of 0.17 cm ² /Vs, which is classified into the highest class of field-effect mobility of organic thin films.     

Perimidine-based synthetic receptors for determination of copper(II) in water solution

Perimidine-based chelators 1 and 2 were prepared, and their structures were confirmed by ¹H and ¹³C NMR, MS spectroscopy and elemental analysis. These compounds were studied as specific synthetic receptors for the recognition of transition metal ions. They exhibited high affinity and selectivity towards Cu(II) ions. The conditional binding constants, linear dynamic range and detection limit were determined by UV–vis spectroscopy. These parameters demonstrated high potential of the prepared synthetic receptors for the recognition and determination of Cu(II) ions. The minimum detectable concentrations of Cu(II) ions for the synthetic receptors 1 and 2 were 270 and 75 nM (R ² = 0.9915 and 0.9964) in aqueous medium (water/DMSO; 99:1 (v/v)), respectively.     

The Mechanism and Stereochemistry of Wittig Reactions of Phosphonium Ylide-Anions

Abstract

Schmidbaur's group have extensively investigated¹ the coordination properties of phosphonium 1,3-ylide-anions (1) in organometallic chemistry and more recently Cristau² has reported the potential usefulness of these compounds in synthetic organic chemistry. There have been a few studies³ of specific phosphonium 1,1-ylide-anions (2), however their only use in the Wittig reaction appears to be that of (2a).⁴ We have set out to study the stereochemistry and mechanism of Wittig reactions of (1) and (2) and to carry out some preliminary investigations on the arsenic analogues (3).     

High Yield Synthesis and Preliminary Spectroscopic Study of Mono-N-alkylated Cyclen Derivatives of Salicylic Acid

Selective and high yield synthesis of N-substituted salicylic acid derivatives of cyclen has been achieved by using a direct synthetic procedure under mild reaction conditions. The protonation constants of these compounds were determined by potentiometric titration. The complexing properties of the cyclen derivatives with metal cations were investigated by UV–Vis spectroscopy and ¹H NMR. The stability constants of Mg²⁺, Ca²⁺ and Sr²⁺ complexes with ligands 5 and 6 were determined.     

Synthesis of 2-Nitrocyclopentanone

The synthetic utility of cyclic α-nitroketones as well as the preparation of these useful synthetic intermediates has recently been reviewed¹. Although the dipotassium salt of 2,5-dinitrocyclopentanone has been synthesized², 2-nitrocyclopentanone itself could not be prepared by nitrating cyclopentanone with an alkyl nitrate and either potassium amide in liquid ammonia² or potassium t-butoxide in tetrahydrofuran³. Furthermore, the reaction of 1-bromocyclopentene with dinitrogen tetroxide led only to a 15–20% yield of 2-nitrocyclopentanone as the 2,4-dinitrophenylhydrazone derivative⁴. The lone report of an actual preparation of 2-nitrocyclopentanone appears in a patent however with no characterization of the compound⁵. We now wish to report the synthesis and characterization of 2-nitrocyclopentanone, a potential versatile synthetic intermediate. Starting with cyclopentanone we have achieved the synthesis of the title compound by three methods outlined in Scheme I.     

Synthesis of Glycosyl Esters and Glycosyl Hemiacetals From Methylthioglycosides

ABSTRACT

Glycosyl esters constitute a widespread family of natural products such as anti-tumor agents,¹ antibiotics,² terpenoid glycosides,³ plant pigments⁴ and other substances.⁵ It has been shown that aromatic carboxylic acids are metabolized by humans as glycosyl esters,⁶ and D-glucopyranosyl fatty acid esters were found to inhibit the growth of leukemia cells⁷ and plant growth.⁸ The synthesis of a prodrug in the g form of a glycosyl ester has been reported.⁹ In synthetic chemistry glycosyl acetates are frequently used glycosyl donors in Lewis-acid catalyzed glycosylation reactions¹⁰ and other transformations.¹¹     

Palladium(II)-assisted ortho alkylation of C(sp2)-H bonds in substituted azobenzenes with simple alkyl halides

Abstract

A new and relatively simple synthetic strategy has been described for Pd(II)-catalyzed C-C bond formation via alkylation of ortho C(sp²)-H bonds in substituted azobenzenes possessing (2-phenylamino)phenylazo directing group employing different alkyl iodides. The yields of various ortho alkylated products are found to be good to excellent (65%–85%). A palladocyclic intermediate complex has been isolated and fully characterized. Based on the experimental results and the isolation of the palladocyclic intermediate, a catalytic cycle involving a sequential C-H activation/oxidative addition followed by reductive elimination pathway has been proposed.     

Derivative Spectrophotometric Determination of Copper and Palladium Simultaneously by Using MDTC as a Reagent

Abstract

A selective, sensitive, and economical derivative spectrophotometric method has been developed for the determination of trace amount of Cu(II) and Pd(II) with MDTC as a reagent in the presence of CTAB, a solubilizing agent. The molar absorption coefficient and analytical sensitivities of the 1:2 Cu(MDTC)₂ and Pd(MDTC)₂ complexes are 2.467×10⁴ and 2.989×10⁴ l mol^?1, respectively. The developed derivative procedure, is applied for the rapid and selective simultaneous determination of Cu(II) and Pd(II) in the range of 0.2–15 and 0.1–10 µg/ml, respectively. Complex matrices, including alloys, biological samples, pharmaceutical samples and synthetic mixtures have been successfully analyzed for trace amounts of two metal ions.     

Vinyl Carbanions. Part 36.. Synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO) and derivatives

The β-C-lithiated acrylamide 3A has been proven to be an ideal pyruvate β-carbanion equivalent useful in a highly diastereoselective KDO synthesis. The starting material 3 was prepared from pyruvate diethyl acetal in four convenient steps. Direct lithiation with 2 equiv. of LDA generated the dilithiated species 3A quantitatively. Reaction with 2,3:4,5-di-O-isopropylidene-D -arabinose ( 11 ) was highly D -manno-selective. The product 12 was obtained readily from the reaction mixture via crystallization. Ring closure to the butenolide 13 , subsequent PhS-group removal with Bu₃SnH and pyridinium bromide, and hydrogenolytic debenzylation afforded the known butenolide 19 ; this KDO precursor gives KDO in two convenient steps. Butenolide 19 was also transformed via two high-yielding steps into the 4,5:7,8-di-O-cyclohexylidene-KDO derivative 22 , a valuable starting material for KDO α-glycoside syntheses.     

Chemiluminescence Detection of Amino Acids,Peptides, and Proteins Using Tris-2,2′-Bipyridine Ruthenium (III)

Abstract

The feasibility of using the tris-2-2′-bipyridine ruthenium (III) (Ru(bpy)₃ ^{3 +}) chemiluminescent (CL) reaction for the detection of amino acids, peptides, and proteins has been studied.

Detection limits of the amino acids as determined by flow injection analysis (FIA) ranged from 20 pmol of proline to 50 nmol of asparagine. In general, amino acids containing secondary amine groups yielded the strongest responses. A reaction mechanism for Ru (bpy)₃ ^{3 +} chemiluminescence of aliphatic amines has been proposed. Studies of peptide molecules and poly-prolines showed that the peptide bond barely contributes to the detection signals. The separation of hydroxyproline and proline in synthetic collagen by HPLC with Ru (bpy)₃ ^{3 +} chemiluminescence detection has been shown to be possible.