Synthesis of <Emphasis Type="Italic">N</Emphasis><Superscript>2</Superscript>-Arylisocytidines and <Emphasis Type="Italic">N</Emphasis><Superscript>2</Superscript>-Aryl-2′-deoxyisocytidines

Summary. 2-(Arylamino)pyrimidin-4-ones were synthesized, silylated, and condensed with l,2,3,5-tetra-O-acetyl-β- d-ribofuranoside to afford the corresponding N ²-aryl protected isocytidines. Deprotection of the acetylated isocytidines using saturated NH₃ in MeOH solution gave 1-(β-d-ribofuranosyl)-2-(arylamino)-4-pyrimidinones. Methyl 2-deoxy-3,5-di-O-toluyl-α/β-d-ribofuranoside was prepared and condensed with the previously silylated bases to afford the anomeric mixture of protected nucleosides. The pure β-anomers were synthesized with better yield by treating the sodium salts of N ²-arylisocytosine derivatives with 2-deoxy-3,5-di-O-toluyl-α-d-ribofuranosyl chloride. Deprotection of the latter anomers afforded the corresponding free hydroxyl derivatives. The synthesized free nucleosides are under antiviral and oligonucleotide investigations.     

An easy access to a 3,6-branched mannopentaoside bearing one terminal [1-<Superscript>13</Superscript>C]-labeled <Emphasis Type="SmallCaps">D</Emphasis>-mannopyranose residue

Methyl 2,4-di-O-benzoyl-α-D-mannopyranoside was used as a key intermediate in the synthesis of 3,6-branched mannopentaoside bearing one terminal D-[1-¹³C]mannopyranose residue, viz., methyl 6-O-[3,6-di-O-(α-D-mannopyranosyl)-α-D-mannopyranosyl)-3-O-{α -D-[1-¹³C]mannopyranosyl}-α-D-mannopyranoside. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1250–1255, May, 2005.     

Studies on crystals of <Emphasis Type="SmallCaps">d</Emphasis>-, <Emphasis Type="SmallCaps">l</Emphasis>-, and <Emphasis Type="SmallCaps">dl</Emphasis>-alaninato nickel(II) complexes

An attempt to link the heat of reaction obtained from analysis of UV spectra, bond energies deduced from crystallographic data and calorimetric measurements of [bis(d-, l-, and dl-alaninato)diaqua] nickel(II) dihydrate complexes to theoretical values obtained from calculation is described. The heat of reaction, which includes energy of ligand exchange in addition to crystal field stabilization energy of the three complexes, was calculated from changes in spectral shifts, bond lengths, and free energy between nickel(II) ion and the d-, l-, and dl-alanine complexed nickel(II) ion in aqueous solution. These investigations were done by UV–visible spectroscopy, X-ray crystallography, and isothermal calorimetry. The results reveal that the experimental heat of reaction based on the three mentioned parameters is in good agreement with the theoretical value. The results are found to be of considerable interest in its linking of spectrochemical quantities with thermodynamic functions.     

<Emphasis Type="Italic">O</Emphasis>- and <Emphasis Type="Italic">N</Emphasis>-Alkylation of <Emphasis Type="Italic">N</Emphasis>-halosuccinimides in ionic reactions with 1-phenyltricyclo [4.1.0.0<Superscript>2,7</Superscript>]heptane

N-Bromo and N-chlorosuccinimides add to 1-phenyltricyclo[4.1.0.0^2,7]heptane in CH₂Cl₂ with cleavage of the C(1)-C(7) bond to give isomeric 1 : 1 Markownikoff-type endo, anti-adducts of the norpinane structure in a ∼3 :7 ratio corresponding to N and O alkylation of succinimide.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No.2, pp. 457–460, February, 2005     

Facile synthesis of chiral <Emphasis Type="Italic">N</Emphasis>-glycosylated amino acids

Five designed chiral glycosylated amino acids have been synthesized for the first time by coupling of 1,3,4,6-tetra-O-acetyl-β-D-glucosamine sulfate (2), previously prepared by direct acetylation of D-glucosamine hydrochloride with acetic anhydride, with chiral Fmoc-protected amino acids and DIC, HOBt, and DIEA under mild conditions. The structures of these new compounds were characterized by IR, ¹H NMR, and ¹³C NMR spectroscopy and ESI MS.     

Synthesis and Stereochemistry of 1<Emphasis Type="Italic">H</Emphasis>,5<Emphasis Type="Italic">H</Emphasis>-Naphtho[1,8-<Emphasis Type="Italic">ef</Emphasis>][1,3]dithiocine 2-Oxides

3-Substituted 1H,5H-naphtho[1,8-ef][1,3]dithiocines (R = H, Me, Ph, t-Bu) were oxidized with m-chloroperoxybenzoic acid to the corresponding 2-oxides having trans configuration (R ≠ H). According to the ¹H and ¹³C NMR data (including NOESY experiments), the disubstituted compounds at room temperature exist in a boat conformation with equatorial orientation of the substituent on C³ and oxygen atom on S². The compound with no substituent on C³ gives rise to a mixture of boat conformers with axial and equatorial sulfoxide oxygen atoms at a ratio of 83:17.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1109–1112.Original Russian Text Copyright © 2005 by Kikilo, Khairutdinov, Shtyrlin, Klochkov, Klimovitskii.     

Bioconversion of <Emphasis Type="SmallCaps">d</Emphasis>-glucose into <Emphasis Type="SmallCaps">d</Emphasis>-glucosone by Glucose 2-oxidase from <Emphasis Type="Italic">Coriolus versicolor</Emphasis> at Moderate Pressures

Glucose 2-oxidase (pyranose oxidase, pyranose:oxygen-2-oxidoreductase, EC 1.1.3.10) from Coriolus versicolor catalyses the oxidation of d-glucose at carbon 2 in the presence of molecular O₂ producing d-glucosone (2-keto-glucose and d-arabino-2-hexosulose) and H₂O₂. It was used to convert d-glucose into d-glucosone at moderate pressures (i.e. up to 150 bar) with compressed air in a modified commercial batch reactor. Several parameters affecting biocatalysis at moderate pressures were investigated as follows: pressure, [enzyme], [glucose], pH, temperature, nature of fluid and the presence of catalase. Glucose 2-oxidase was purified by immobilized metal affinity chromatography on epoxy-activated Sepharose 6B-IDA-Cu(II) column at pH 6.0. The rate of bioconversion of d-glucose increased with the pressure since an increase in the pressure with compressed air resulted in higher rates of conversion. On the other hand, the presence of catalase increased the rate of reaction which strongly suggests that H₂O₂ acted as inhibitor for this reaction. The rate of bioconversion of d-glucose by glucose 2-oxidase in the presence of either nitrogen or supercritical CO₂ at 110 bar was very low compared with the use of compressed air at the same pressure. The optimum temperature (55°C) and pH (5.0) of d-glucose bioconversion as well as kinetic parameters for this enzyme were determined under moderate pressure. The activation energy (E _a) was 32.08 kJ mol⁻¹ and kinetic parameters (V _max, K _m, K _cat and K _cat/K _m) for this bioconversion were 8.8 U mg⁻¹ protein, 2.95 mM, 30.81 s⁻¹ and 10,444.06 s⁻¹ M⁻¹, respectively. The biomass of C. versicolor as well as the cell-free extract containing glucose 2-oxidase activity were also useful for bioconversion of d-glucose at moderate pressures. The enzyme was apparently stable at moderate pressures since such pressures did not affect significantly the enzyme activity.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [¹⁸F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [¹⁸F]FET are similar to those of [¹⁸F]FDG, but the ratios of tumor-to-brain (T/Br) are 2–3 times higher than that of [¹⁸F]FDG. Autoradiography of [¹⁸F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET. Supported by the Knowledge Innovation Project of Chinese Academy of Sciences (No. KJCX1-SW-08) and the National Natural Science Foundation of China (Grant No. 30371634)     

Structure of Galactomannans from <Emphasis Type="Italic">Gleditsia delavayi</Emphasis> and <Emphasis Type="Italic">G. aquatica</Emphasis> by <Superscript>1</Superscript>H and <Superscript>13</Superscript>C NMR Spectroscopy

The structure of galactomannans isolated from seeds of G. delavayi and G. aquatica was studied by ¹H and ¹³C NMR spectroscopy. It was found that the galactomannans consisted mainly of β-1-4-bound mannopyranoses, a part of which was substituted on the C-6 hydroxyl by terminal units of α-galactopyranose.__________Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 12–13, January–February, 2005.     

Synthesis of isotopomers of <Emphasis Type="SmallCaps">l</Emphasis>-DOPA and dopamine labeled with hydrogen isotopes in the side chain

The enzymatic synthesis of three isotopomers of l-DOPA labeled with deuterium and tritium at α carbon atom was elaborated. These compounds were converted into [(1S)-²H]–, [(1S)- ³H]–, and doubly labeled [(1S)-²H/³H]-dopamines using enzyme tyrosine decarboxylase. Doubly labeled (1R) isotopologue, i.e., [(1R)-²H/³H]-dopamine, was afforded by enzymatic decarboxylation of authentic l-DOPA carried out in deuteriated and tritiated incubation medium.     

Synthesis and characterization of novel (<Emphasis Type="Italic">E</Emphasis>,<Emphasis Type="Italic">E</Emphasis>)-dioxime and its mono- and polynuclear metal complexes containing azacrown moieties

The novel (E,E)-dioxime,7,8-bis(hydroxyimino)-1,14-bis(monoaza[8]crown-6)-benzo[f]-4,11-dioxa-1,14-diazadecane[7,8-g]quinoxaline (H₂L), has been synthesized by the reaction of 6,7-diamino-1,12-bis(monoaza[18]crown-6)benzo[f]-4,9-dioxa-1,12-diazadecane (4) which has been prepared by the reduction of 6,7-dinitro-1,12-bis(mono-aza[18]crown-6)benzo[f]-4,9-dioxa-1,12-diazdecane (3) and cyanogendi-N-oxide. Mononuclear Ni^II and Cu^II complexes of H₂L have a metal:ligand ratio of 1:2 and the ligand coordinates through two hydroxyimino nitrogen atoms, as do most of the (E,E)-dioximes. The hydrogen-bridged Ni^II complex was converted into its BF ₂ ⁺ capped anologue by the reaction with BF₃ · Et₂O. The reaction of the Cu^II complex with 2,2′-dipyridyl as an end-cap ligand gave the homotrinuclear complex. Structures for the ligand and its complexes are proposed in accordance with elemental analysis, magnetic susceptibility measurements, ¹H, ¹³C-n.m.r, IR and MS spectral data.     

Structure elucidation of uniformly <Superscript>13</Superscript>C-labeled bacterial celluloses from different <Emphasis Type="Italic">Gluconacetobacter xylinus</Emphasis> strains

The morphological and supramolecular structures of native cellulose pellicles from two strains of Gluconacetobacter xylinus (ATCC 53582, ATCC 23769) were investigated. Samples had been statically cultivated in Hestrin-Schramm medium containing fully ¹³C-labeled β-d-glucose-U-¹³C₆ as the sole source of carbon. The results are compared with structure data of bacterial celluloses with a natural ¹³C abundance of 1.1%. Non-enriched and ¹³C-labeled cellulose pellicles formed crystalline structures as revealed by cross-polarized/magic-angle spinning (CP/MAS) ¹³C{¹H}-NMR and near infrared (NIR) FT-Raman spectroscopic measurements as well as wide-angle X-ray diffraction (WAXD) investigations. Atomic force microscopy (AFM) was applied for analyzing fiber morphologies and surface properties. For the first time, details about the manipulation of fiber widths and pellicle formation were shown for different bacterial strains of G. xylinus depending on the use of β-d-glucose-U-¹³C₆ for the biosynthesis.     

Enantioselective analysis of (<Emphasis Type="Italic">R</Emphasis>)- and (<Emphasis Type="Italic">S</Emphasis>)-carvedilol in human plasma by high-performance liquid chromatography

Summary An HPLC column-switching method has been developed and validated for the enantioselective determination of (R)- and (S)-carvedilol in human plasma. Sample preparation was performed either off-line, by extraction with trichloromethane and back-extraction into 0.01m aqueous citric acid which was injected on to a LiChrosorb RP 8 column, or on-line, by injecting diluted (0.1m formic acid) plasma on to a LiChrosorb ADS column. In both instances separation was performed by gradient elution and on-line transfer of the fraction containing, the carvedilol on to an enantioselective Teicoplanin column. The enantiomers of carvedilol were separated isocratically by use of methanol-acetonitrile-triethylammonium acetate, 70:30:0.05 (v/v/w), as mobile phase. With fluorescence detection the limits of quantitation were 0.30 ng mL⁻¹ for (R)-carvedilol and 0.26 ng mL⁻¹ for (S)-carvedilol; these were sufficient to enable investigation of the effect of exercise on plasma concentrations of (R)- and (S)-carvedilol after oral administration of either the racemate or the pure enantiomers. Although the operating conditions were optimized for sample preparation by on-line deproteination on a LiChrospher RP 18 ADS column, the complete method was insufficiently rugged for analysis of large numbers of plasma samples—the enantioselectivity of the Teicoplanin column deteriorated too rapidly because of the transfer of enantioselectivity-poisoning interferences which could not be suppressed sufficiently. In contrast the liquid-liquid sample-extraction procedure combined with column switching resulted in a analytical method with long-term stability. Presented at Balaton Symposium '01 on High-Performance Separation Methods, Siófok, Hungary, September 2–4, 2001     

Association behavior of one-end hydrophobically modified poly[<Emphasis Type="Italic">N</Emphasis><Superscript>5</Superscript>-(2-hydroxyethyl) <Emphasis Type="SmallCaps">l</Emphasis>-glutamine] in water/ethylene glycol mixed solvent

Amphiphilic polymers Cn-PHEG consisting of water-soluble poly[N ⁵-2-(hydroxyethyl) l-glutamine] (PHEG) and hydrophobic alkyl chain (carbon number n = 12, 14, 16, or 18) attached at the PHEG terminal was prepared, and association behavior and structure of associate for Cn-PHEG in selective solvent (water/ethylene glycol mixed solvent) have been investigated. α-Helix content of PHEG block for all the polymers increased with weight fraction of ethylene glycol in the mixed solvent (W _EG). By light scattering measurements, formation of a small micelle was suggested for C14-, C16-, and C18-PHEG when W _EG = 0. With the increase in W _EG, appearance of a larger associate was revealed for C16- and C18-PHEG. Evaluated molecular weight and radius of gyration suggested that the micelle is star-like sphere when W _EG = 0 and worm-like cylinder when W _EG = 0.7. C12-PHEG did not demonstrate any distinct micellization behavior because of the weak hydrophobicity of C12 chain.     

Synthesis and some properties of neodymium(<Emphasis Type="SmallCaps">III</Emphasis>) and dysprosium(<Emphasis Type="SmallCaps">III</Emphasis>) iodide hydrides LnI<Subscript>2</Subscript>H

The iodide hydrides NdI₂H (1) and DyI₂H (2) were obtained by the reactions of diiodides NdI₂ (3) and DyI₂ (4) with hydrogen at atmospheric pressure and temperature of 120–200 °C. Hydrolysis of products 1 and 2 gives hydrogen in a high yield. The reactions of 1 with phenol and of 2 with isopropyl alcohol in THF afford the iodide phenoxide NdI₂(OPh)(THF)₄ and iodide isopropoxide DyI₂(OPrⁱ)(PrⁱOH)₃, respectively. The reaction of 2 with cyclopentadiene is accompanied by disproportionation and gives, besides dihydrogen, Cp₂DyI(THF)₂ and DyI₃(THF)₃. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1887–1889, October, 2007.     

Reaction of iodo(trimethyl)silane with <Emphasis Type="Italic">N,N</Emphasis>-dimethyl carboxylic acid amides

The reactions of iodo(trimethyl)silane with N,N-dimethylformamide and N,N-dimethylacetamide Me₂NCOR (R = H, Me) at a molar ratio of 1: 2 involved mainly cleavage of the N-C(=O) bond with formation of up to 80% of N,N-dimethyltrimethylsilylamine Me₃SiNMe₂ and the corresponding acyl iodide RCOI. In the reaction with N,N-dimethylformamide, formyl iodide HCOI was detected for the first time by gas chromatography-mass spectrometry. The contribution of Me-N bond cleavage, leading to N-methyl-N-trimethylsilyl derivative Me(Me₃Si)NCOR and methyl iodide was considerably smaller. Another by-product was the corresponding N-methyl imide MeN(COR)₂ formed by reaction of the initial amide with acyl iodide. The primary intermediate in the reaction of iodo(trimethyl)silane with DMF and DMA is quaternary ammonium salt [Me₂(Me₃Si)N⁺COR] I⁻ which decomposes via dissociation of the N-CO and N-Me bonds.     

Complexation of Cu(II) with <Emphasis Type="SmallCaps">L</Emphasis>- and <Emphasis Type="SmallCaps">DL</Emphasis>-threonine: An ESR study

Complexation of Cu(II) ions with L- and DL-threonine in aqueous solution was studied. Treatment of the ESR spectra of solutions containing Cu(II) and threonine in various ratios and having various pH, involving total line shape analysis, revealed formation of geometric isomers of the complex ions [Cu(thrH_–1)₂]^2– differing in the mutual arrangement of the N and O atoms in the equatorial plane; the complexation and isomerization equilibrium constants were determined.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 8, 2004, pp. 1388–1391.Original Russian Text Copyright © 2004 by Statsenko, Bolotin, Panyushkin.This revised version was published online in April 2005 with a corrected cover date.     

<Emphasis Type="Italic">N,N′</Emphasis>-Bis(triethoxysilylmethyl)thiocarbamide and Poly[<Emphasis Type="Italic">N,N′</Emphasis>-bis(silsesquioxanylmethyl)thiocarbamide <Emphasis Type="Italic">S,S</Emphasis>-dioxide]

Condensation of (aminomethyl)triethoxysilane with thiocarbamide in the presence of catalytic amounts of ammonium sulfate was used to synthesize N,N-bis(triethoxysilylmethyl)thiocarbamide. The latter was brought into oxidative hydrolytic polycondensation with H₂O₂ to obtain poly[N,N′-bis(silsesquioxanylmethyl)thiocarbamide S, S-dioxide] whose properties were compared with the properties of poly[N,N′-bis(silsesquioxanylpropyl)thiocarbamide S,S-dioxide]. Both polymers in highly acidic media rather strongly absorb Ag(I), while at pH 7 they reduce most absorbed Ag⁺ to the metal. Their reaction with potassium permanganate involves reduction of Mn⁷⁺ to Mn⁴⁺. The first polymer is a less effective sorbent and redox agent than the second.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 7, 2005, pp. 1154–1156.Original Russian Text Copyright © 2005 by Voronkov, Vlasova, Grigor’eva, Pozhidaev, Bol’shakova.     

Kinetics and mechanism of oxidation of <Emphasis Type="SmallCaps">l</Emphasis>-cystine by manganese(III) in sulfuric acid medium

The kinetics of oxidation of l-cystine by Mn^III have been studied in sulfuric acid medium at 30 °C. The reaction was followed spectrophotometrically at λmax = 500 nm. The reaction shows first order dependence on both [Mn^III] and [cystine]. It was found that the rate of the reaction decreases with increase of [H⁺] up to a certain point and then remains unchanged. The oxidation product of the reaction was found to be cysteic acid. A plausible mechanism has been proposed to account for the experimental results.     

Enhanced Production of <Emphasis Type="SmallCaps">l</Emphasis>-Arginine by Expression of <Emphasis Type="Italic">Vitreoscilla</Emphasis> Hemoglobin Using a Novel Expression System in <Emphasis Type="Italic">Corynebacterium crenatum</Emphasis>

Corynebacterium crenatum SYPA 5-5 is an aerobic and industrial l-arginine producer. It was proved that the Corynebacterium glutamicum/Escherichia coli shuttle vector pJC1 could be extended in C. crenatum efficiently when using the chloramphenicol acetyltransferase gene (cat) as a reporter under the control of promoter tac. The expression system was applied to over-express the gene vgb coding Vitreoscilla hemoglobin (VHb) to further increase the dissolved oxygen in C. crenatum. As a result, the recombinant C. crenatum containing the pJC-tac-vgb plasmid expressed VHb at a level of 3.4 nmol g⁻¹, and the oxygen uptake rates reached 0.25 mg A₅₆₂⁻¹ h⁻¹ which enhanced 38.8% compared to the wild-type strain. Thus, the final l-arginine concentration of the batch fermentation reached a high level of 35.9 g L⁻¹, and the biomass was largely increased to 6.45 g L⁻¹, which were 17.3% and 10.5% higher than those obtained by the wild-type strain, respectively. To our knowledge, this is the first report that the efficient expression system was constructed to introduce vgb gene increasing the oxygen and energy supply for l-arginine production in C. crenatum, which supplies a good strategy for the improvement of amino acid products.