Isobutyl Derivative Research Articles

Identification and Determination of 1,3-Thiazinane-4-carboxylic Acid in Human Urine-Chromatographic Studies.

It is well established that homocysteine (Hcy) and its thiolactone (HTL) are reactive towards aldehydes in an aqueous environment, forming substituted thiazinane carboxylic acids. This report provides evidence that Hcy/HTL and formaldehyde (FA) adduct, namely 1,3-thiazinane-4-carboxylic acid (TCA) is formed in vivo in humans. In order to provide definitive proof, a gas chromatography–mass spectrometry (GC–MS) based method was elaborated to identify and quantify TCA in human urine. The GC–MS assay involves chemical derivatization with isobutyl chloroformate (IBCF) in the presence of pyridine as a catalyst, followed by an ethyl acetate extraction of the obtained isobutyl derivative of TCA (TCA-IBCF). The validity of the method has been demonstrated based upon United States Food and Drug Administration recommendations. The assay linearity was observed within a 1–50 µmol L−1 range for TCA in urine, while the lowest concentration on the calibration curve was recognized as the limit of quantification (LOQ). Importantly, the method was successfully applied to urine samples delivered by apparently healthy volunteers (n = 15). The GC–MS assay may provide a new analytical tool for routine clinical analysis of the role of TCA in living systems in the near future.

Phase control during the synthesis of nickel sulfide nanoparticles from dithiocarbamate precursors.

Square-planar nickel bis(dithiocarbamate) complexes, [Ni(S2CNR2)2], have been prepared and utilised as single source precursors to nanoparticulate nickel sulfides. While they are stable in the solid-state to around 300 °C, heating in oleylamine at 230 °C, 5 mM solutions afford pure α-NiS, where the outcome is independent of the substituents. DFT calculations show an electronic effect rather than steric hindrance influences the resulting particle size. Decomposition of the iso-butyl derivative, [Ni(S2CN(i)Bu2)2], has been studied in detail. There is a temperature-dependence of the phase of the nickel sulfide formed. At low temperatures (150 °C), pure α-NiS is formed. Upon raising the temperature, increasing amounts of β-NiS are produced and at 280 °C this is formed in pure form. A range of concentrations (from 5-50 mM) was also investigated at 180 °C and while in all cases pure α-NiS was formed, particle sizes varied significantly. Thus at low concentrations average particle sizes were ca. 100 nm, but at higher concentrations they increased to ca. 150 nm. The addition of two equivalents of tetra-iso-butyl thiuram disulfide, ((i)Bu2NCS2)2, to the decomposition mixture was found to influence the material formed. At 230 °C and above, α-NiS was generated, in contrast to the results found without added thiuram disulfide, suggesting that addition of ((i)Bu2NCS2)2 stabilises the metastable α-NiS phase. At low temperatures (150-180 °C) and concentrations (5 mM), mixtures of α-NiS and Ni3S4, result. A growing proportion of Ni3S4 is noted upon increasing precursor concentration to 10 mM. At 20 mM a metastable phase of nickel sulfide, NiS2 is formed and as the concentration is increased, α-NiS appears alongside NiS2. Reasons for these variations are discussed.

A Practical Synthetic Approach to Chiral (α-Chloroalkyl)boronic Esters via Iridium-Catalyzed Chemoselective Hydrogenation of Chloro-Substituted Alkenyl Boronates

Chiral (α-chloroalkyl)boronic esters are obtained by homogeneous asymmetric iridium-catalyzed chemoselective hydrogenation of (1-chloro-1-alkenyl)boronic esters. P,N–Iridium catalysis provides low level of dehalogenation during the hydrogenation, while the catalyst activity and enantioselectivity essentially depends on the applied P,N ligand features. Fine tuning of P,N ligand structures enables high conversions, broad substrate acceptance, and high to excellent enantioselectivities with enantiomeric excess values up to 94% along with low levels of dechlorination. Low catalyst loading with S/C = 200 can also be achieved for the preparation of an industrially important isobutyl derivative.

Monoalkylaluminium Complexes Stabilized by a Rigid Dianionic Diimine Ligand: Synthesis, Solid State Structure, and Dynamic Solution Behaviour of (dpp‐BIAN)AlR (R = Me, Et, iBu)

Abstract(dpp‐BIAN)Na2 (dpp‐BIAN = 1,2‐bis[(2,6‐di‐iso‐propylphenyl)imino]acenaphthene) reacts with two equivalents of R2AlCl in Et2O to give the monoalkylaluminium complexes (dpp‐BIAN)AlR(Et2O) (R = Me, 1; Et, 2; iBu, 3). Compounds 1‐3 have been characterized by elemental analysis, IR and 1H NMR spectroscopy. Single crystal X‐ray diffraction has been used to determine the molecular structures of 1 and 2. Both structures show the aluminium atom tetrahedrally coordinated by the two N atoms of the dianionic dpp‐BIAN ligand, the alkyl group, and a diethyl ether molecule. Temperature dependent 1H NMR spectroscopic measurements of 2 in THF‐d8 revealed a dynamic process caused by positional exchange between the ethyl group and the ether molecule relative to the metallacycle, which slows down with decreasing temperature. In the case of the methyl derivative 1, the corresponding process is fast at ambient as well as at low temperatures, whereas in the case of the isobutyl derivative 3 the larger size of the alkyl group prevents such a positional ligand exchange already at room temperature.

E-Ring Modified Steroids as Novel Potent Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1

17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) are an important class of steroidogenic enzymes that regulate the bioavailability of active estrogens and androgens and are as yet a relatively unexploited therapeutic target. Based on our investigations and those of others, E-ring modified steroids were identified as a useful template for the design of inhibitors of 17beta-HSD type 1, an enzyme involved in the conversion of estrone into estradiol. The synthesis and biological evaluation of a new series of N- and C-substituted 1,3,5(10)-estratrien-[17,16-c]-pyrazoles and the corresponding SAR are discussed. Among the N-alkylated analogues, the most potent inhibitor was the 1'-methoxyethyl derivative, 41, with an IC(50) of 530 nM in T47-D human breast cancer cells. The X-ray crystal structure of the 1'-isobutyl derivative, was determined. Further optimization of the template using parallel synthesis resulted in a library of C5'-linked amides from which 73 emerged. This pyridylethyl amide had an IC(50) of 300 nM and its activity, with that of 41, suggests the importance of hydrogen bond acceptor groups in the pyrazole side chain. Both 41 and 73 displayed selectivity over 17beta-HSD type 2, and preliminary investigations showed 41 to be nonestrogenic in vitro in a luciferase reporter gene assay in contrast to the parent pyrazole 25. Molecular modeling studies, which support these findings, and a QSAR, the predictive power of which was demonstrated, are also presented.

Neutral, Three-Coordinate, Chelating Diamide Aluminum Complexes: Catalysts/Initiators for Synthesis of Telechelic Oligomers and High Polymers

Reaction of the bulky chelating diamine ligand ArNH(CH2)3NHAr (Ar = 2,6-iPr2C6H3) with AlMe3 cleanly affords the monomeric, three-coordinate, chelating diamide aluminum complex [N∩N]AlMe (1). The isobutyl derivative [N∩N]AliBu (2) is prepared in the same manner using triisobutylaluminum. The Al/B alkyl/aryl ligand exchange between 1 and B(C6F5)3 in refluxing toluene cleanly produces the pentafluorophenyl-substituted derivative [N∩N]AlC6F5 (3). Studies of model reactions between 1 and e-caprolactone as well as analyses of low-molecular-weight oligomers demonstrate the ability of 1 to produce telechelic oligomers. At high monomer/initiator ratios, all three complexes are active for ring-opening polymerization of e-caprolactone and cyclohexene oxide, producing high-molecular-weight polymers. The isobutyl derivative 2 exhibits the highest activity for both polymerizations in this catalyst series and produces poly(e-caprolactone) having a number-average molecular weight over 1,000,000 Da.

Aluminium compounds containing bidentate ligands: chelate ring size and rigid conformation effects

Reaction of Al(tBu)3 with 2-hydroxypyridine, 2-pyridinemethanol, 8-hydroxyquinoline and 8-quinolinemethanol, yielded [(tBu)2Al(µ-O-2-C5H4N)]2 1, (tBu)2Al(OCH2-2-C5H4N) 2, (tBu)2Al(O-8-C9H6N) 3 and (tBu)2Al(OCH2-8-C9H6N) 4, respectively. The isobutyl derivative, [(iBu)2Al(µ-O-8-C9H6N)]2 5, was prepared in an analogous manner. The molecular structures of compounds 1, 3 and 5 have been determined by X-ray crystallography. Compounds 2–4 are monomeric with five (2 and 3) and six (4) membered chelate heterocyclic rings. In contrast, compound 1 and 5 exist as bridged dimers. The isobutyl groups on each of the aluminium centers in compound 5 are in an anti conformation both in the solid state and solution. The activation energy for the interconversion of the two anti enantiomers has been determined [ΔG ‡ = 68.5(4) kJ mol–1]. The formation of monomeric chelate compounds for compounds 2–4, rather than alkoxide bridged dimers as is found for (iBu)2Al(OCH2-2-C5H4N) and 5 is found to be due to a combination of the steric bulk of the aluminium alkyl and the rigid conformation of the pyridine and quinoline ligands.

Studies of iron transport in wheat using synthetic phytosiderophores

Abstract Synthetic phytosiderophores based on deoxydistichonic acid A have been made. The molecules synthesized so far include deoxydistichonic acid A itself (designated PS1), a more hydrophobic isobutyl derivative (PS2), an acidic analogue (PS3), and a basic analogue (PS4). Both PS1 and PS2 have been shown to promote the uptake of 59Fe into iron‐deficient wheat and the rates of uptake are comparable to those measured with the natural phytosiderophore, 2 ‐deoxymugineic acid (DMA). Rates of uptake were maximal after about 12–14 d of iron deprivation and variability between experiments was decreased when such young plants were used. These synthetic compounds and other structural analogues will be used to study the structure‐function relations of phytosiderophores, and to affinity label the transporter molecule.

Notizen: Zinnorganische Fluoride als Fluorierungsreagenzien für Chloride von Hauptgruppenelementen - Quantitatives Recycling des Fluorierungsreagenzes / Tinorganic Fluorides Function as Fluorinating Reagents for Chlorides of Main Group Elements - Quantitative Recycling of the Fluorinating Reagent

Abstract PF3 is obtained in high purity by reacting PCl3 with Me3SnF. Alternative fluorinating reagents for this reaction are Ph3SnF and (i-C4H9)3SnF. The reaction with the isobutyl derivative is less complicated since the resulting chloride is a liquid in contrast to Ph3SnCl being a solid. PCl5, MeCOCl, SiCl4, Me3SiCl, and SOCl2 react with Me3SnF to give also the corresponding fluorides. The resulting chlorides are easily converted again to the fluorides. A quantitative recycling of the fluorinating reagent is therefore achieved.

Crystal structures, molecular conformations, hydrogen bonds, and 35Cl NQR in some chloral hemiacetals

AbstractCrystal structures of chloral 4‐bromo‐, 4‐methyl‐, 2,4‐dichlorobenzylhemiacetals, and iso‐butylhemiacetal were determined by the single crystal X‐ray method at room temperature. Two modifications were found for the 2,4‐dichlorobenzyl derivative. A chiral chain of molecules formed by OH … O hydrogen bonds (H‐bonds) along a 21 axis is common to the crystals studied, except for iso‐butyl derivative where a centrosymmetric dimer is formed by H‐bonds. Conformation analyses were made using molecular mechanics. The crystal structures and IR spectra indicated that the H‐bonds in these crystals except for the 2,4‐dichlorobenzyl derivate were bifurcated ones. An intramolecular OH…Cl interaction was found in the iso‐butyl derivative. The relationship between the 35Cl NQR spectrum and the molecular structure are discussed.

Lanthanoiden‐Komplexe, IV. Alkyl‐und Donor‐substituierte Cyclopentadienyl‐Komplexe des Neodyms

Complexes of the Lanthanides, IV[1]. — Alkyl‐and Donor‐substituted Cyclopentadienyl Complexes of NeodymiumNeodymium trichloride reacts with the potassium salt K(DoCH2CH2Cp) (2c, DoOMe; 2d, DoNMe2) of the functionalized cyclopentadienyls in THF to yield the sublimable homoleptic complexes Nd(DoCH2CH2Cp)3 (3c, d). Under the same conditions, K(iBuCp) (2a) yields the adduct Nd(i1‐BuCp)3(THF) (3a′), which is obtained free of THF by thermal treatment. The silylamide route is applied to synthesize the homoleptic neopentylcyclopentadienyl derivative Nd‐(NeopCp)3 (3b). The alkyl‐substituted complexes, particularly the isobutyl derivative, show a remarkable volatility. The first solvent‐free, monomeric complex of the type „LnCp2Cl”︁, namely Nd(Me2NCH2CH2Cp)2Cl (4), is obtained from NdCl3 and two equivalents of 2d.

Two-dimensional gas chromatography with electron-capture detection used in the determination of specific peptidoglycan and lipopolysaccharide constituents of gram-negative bacteria in infected human urine.

Gas chromatography with electron-capture detection was used in the determination of diaminopimelic acid (as the N-heptafluorobutyryl isobutyl derivative) and 3-hydroxymyristic acid (as the O-pentafluorobenzoyl methyl derivative) in Gram-negative bacterial cells in infected human urine. Use of the column-switching (two-dimensional gas chromatography) technique greatly enhanced the selectivity of the detection and simplified the processing of samples. The system described should prove useful for trace detection of specific bacterial constituents in complex environments.

The thermal degradation of zinc O,O‐dialkyl phosphorodithioates and related compounds in petroleum media. Part 1. Zinc O,O‐diisobutyl phosphorodithioate

AbstractThe thermal decomposition of zinc O,O‐dialkyl phosphorodithioates is acknowledged to play a significant part in their activity as multipurpose lubricating oil additives. Therefore, the isobutyl derivative in pentadecane solution has been degraded in a novel apparatus under a nitrogen atmosphere. The principal volatile products were found by gas‐liquid chromatography and mass spectrometry to be O,O,S‐triisobutyl phosphorodithioate, isobutanethiol and isobutene. In addition to these volatile products a solid (insoluble in organic solvents) was formed. This contained virtually all the zinc in the original reactant and had a zinc: phosphorus ratio of 2:3. It also contained carbon, hydrogen, sulphur and oxygen but the proportions of the latter two elements were unreliable. Variation of the period of heating, the temperature from 176 to 240°C and the concentration of the reactant from 1.4 to 7.0 × 10−2M affected the relative proportion but not the nature of the products formed. An equation involving the reaction of two molecules of the reactant has been written but kinetic data is required in order to establish a mechanism.