2219-51-4Relevant academic research and scientific papers
Tandem Mass Spectrometric Approaches for the Analysis of Alkylguanines in Human Urine
Cushnir, J. R.,Naylor, S.,Lamb, J. H.,Farmer, P. B.
, p. 552 - 558 (1993)
Human exposure to carcinogenic alkylating agents can lead to the formation of covalently bound adducts in DNA, some of which are excreted in urine as alkylated purines following DNA degradation and repair.Tandem mass spectrometric methods have been developed for the qualitative and quantitative determination of such alkylpurines in human urine.Short-chain alkyl- and hydroxyalkylguanines have been synthesized with the substituents at the N-7, O6- and N2-positions of guanine.Examination of the product ion scans of their molecular ions (electron impact (EI) ionization) revealed that the ion at m/z 151, +, was common to all of the alkylguanines studied, with the exception of the methylated analogues.Precursor ion scans of this ion on partially purified human urine extracts showed the presence of several ions (e.g. m/z 179, 195) which were consistent with molecular ions for alkylguanines.The presence of these and other constituents was confirmed by product ion spectra of molecular ions (EI and fast atom bombardement), and by high-performance liquid chromatographic separation prior to tandem mass spectrometry (MS/MS).Evidence was obtained for the presence of N-7-methyl-, N2-methyl, N2-dimethyl-, N2-ethyl- and N-7-(2-hydroxyethyl)guanine.Quantitative methods were established for these five alkylguanines using gas chromatography mass spectrometry (GC/MS) and GC/MS/MS.Deuterated internal standards were synthesized and added to the urine prior to extraction of alkylpurines by Sep-Pak cartridge chromatography.The products were converted into their tert-butyldimethylsilyl derivatives and analysed by selected ion monitoring (SIM) of + or by multiple reaction monitoring (MRM) of the fragmentation M+. -> +.The MRM method yielded values for N-7-methylguanine of 2.57 +/- S.D. 1.32 mg day-1 (n=6), N2-methylguanine of 0.31 +/- 0.10 mg day-1 (n=10) and N2-dimethylguanine of 0.21 +/- 0.23 mg day-1 (n=10).N2-Ethyl- and N-7-(2-hydroxyethyl)guanine could only be detected by SIM at levels of ca. 0.5 and 2 μg day-1, respectively.The MRM analyses, although inherently less sensitive than the SIM analyses, exhibit greater selectivity and consequently fewer contaminant ions.
Enantiomeric and enantiotopic analysis of cone-shaped compounds with C3 and C3v symmetry using NMR spectroscopy in chiral anisotropic solvents
Lesot, Philippe,Merlet, Denis,Sarfati, Muriel,Courtieu, Jacques,Zimmermann, Herbert,Luz, Zeev
, p. 10071 - 10082 (2002)
We describe the enantiomeric and enantiotopic analysis of the NMR spectra of compounds derived from the functionalized cone-shaped core, cyclotriveratrylenes (CTV), dissolved in weakly oriented lyotropic chiral liquid crystals (CLCs) based on organic solutions of poly-γ-benzyl-L-glutamate. The CTV core lacks prostereogenic as well as stereogenic tetrahedral centers. However, depending on the pattern of substitution, chiral and achiral compounds with different symmetries can be obtained. Thus, symmetrically nonasubstituted CTVs (C3 symmetry) are optically active and exhibit enantiomeric isomers, while symmetrically hexasubstituted (C3v symmetry) derivatives are prochiral and possess enantiotopic elements. In the first part we use 2H and 13C NMR to study two nonasubstituted (-OH or -OCH3) CTVs, where the ring methylenes are fully deuterated, and show for the first time that the observation of enantiomeric discrimination of chiral molecules with a 3-fold symmetry axis is possible in a CLC. It is argued that this discrimination reflects different orientational ordering of the M and P isomers, rather than specific chiral short-range solvent-solute interactions that may affect differently the magnetic parameters of the enantiomers or even their geometry. In the second part we present similar measurements on hexasubstituted CTV with flexible side groups (-OC(O)CH3 and the, partially deuterated bidentate, -OCH2CH2O-), having on the average C3v symmetry. No spectral discrimination of enantiotopic sites was detected for the -OC(O)CH3 derivative. This is consistent with a recent theoretical work (J. Chem. Phys. 1999, 111, 6890) that indicates that in C3v molecules no chiral discrimination between enantiotopic elements, based on ordering, is possible. In contrast, a clear splitting was observed in the 2H spectra of the enantiotopic deuterons of the side groups in the tri(dioxyethylene)-CTV. It is argued that this discrimination reflects different ordering characteristics of the various, rapidly (on the NMR time scale) interconverting conformers of this compound. Assuming two twisted structures for each of the dioxyethylene side groups, four different conformers are expected, comprising two sets of enantiomeric pairs with, respectively, C3 and C1 symmetries. Differential ordering and/or fractional population imbalance of these enantiomeric pairs leads to the observed spectral discrimination of sites in the side chains that on average form enantiotopic pairs.
Regioselective deuteration of alcohols in D2O catalysed by homogeneous manganese and iron pincer complexes
Kar, Sayan,Goeppert, Alain,Sen, Raktim,Kothandaraman, Jotheeswari,Surya Prakash
supporting information, p. 2706 - 2710 (2018/07/05)
We report a convenient and cost-effective protocol for the regioselective deuteration of primary and secondary alcohols using Earth abundant homogeneous first row transition metal pincer catalysts. D2O is utilized as both a deuterium source and a solvent, allowing for a benign inexpensive process. Depending on the metal selected (Mn or Fe), a high degree of deuterium incorporation was observed selectively either at the α and β position (Mn) or exclusively at the α position (Fe), for primary alcohols. This simple, efficient, and cost-effective protocol for alcohol C-H bond deuteration constitutes a powerful tool for the large scale synthesis of deuterated molecules.
Catalytic hydrogenation of cyclic carbonates: A practical approach from CO2 and epoxides to methanol and diols
Han, Zhaobin,Rong, Liangce,Wu, Jiang,Zhang, Lei,Wang, Zheng,Ding, Kuiling
supporting information, p. 13041 - 13045 (2013/03/13)
As an economical, safe and renewable carbon resource, CO2 turns out to be an attractive C1 building block for making organic chemicals, materials, and carbohydrates.[1] From the viewpoint of synthetic chemistry,[2] the utilization of CO2 as a feedstock for the production of industrial products may be an option for the recycling of carbon.[3] On the other hand, the transformation of chemically stable CO2 represents a grand challenge in exploring new concepts and opportunities for the academic and industrial development of catalytic processes.[4] The catalytic hydrogenation of CO2 to produce liquid fuels such as formic acid (HCO 2H)[5] or methanol[6] is a promising solution to emerging global energy problems. Methanol, in particular, is not only one of the most versatile and popular chemical commodities in the world, with an estimated global demand of around 48 million metric tons in 2010, but is also considered as the key to weaning the world off oil in the future.[6e, f] Although the production of methanol has already been industrialized by the hydrogenation of CO with a copper/zinc-based heterogeneous catalyst at high temperatures (250-300°C) and high pressures (50-100 atm),[6e, 7] the development of a practical catalytic system for the hydrogenation of CO2 into methanol still remains a challenge, as high activation energy barriers have to be overcome for the cleavage of the C=O bonds of CO2, albeit with favorable thermodynamics.[8] Heterogeneous catalysis for the hydrogenation of CO 2 into CH3OH has been extensively investigated, and Cu/Zn-based multi-component catalyst was found to be highly selective with a long life, but under relatively harsh reaction conditions (250 °C, 50 atm).[3b, 6d] Therefore, the production of methanol from CO2 by direct hydrogenation under mild conditions is still a great challenge for both academia and industry.
CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR
-
Page/Page column 46-47, (2011/02/24)
The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.
Kinetics and mechanism of the oxidation of diols by butyltriphenylphosphonium dichromate
Panday, Dinesh,Kothari, Seema
body text, p. 918 - 925 (2011/09/19)
The oxidation of four vicinal, four non-vicinal diols and one of their monoethers by butyltriphenylphosphonium dichromate (BTPPD), in dimethylsulfoxide (DMSO), resulted in the formation of corresponding hydroxyaldehyde as a main product of the oxidation. The reactions are of first order with respect to BTPPD, however, second order dependence is obtained with respect to each the diol and hydrogen ion. The oxidation of [1,1,2,2-2H 4]ethanediol exhibited primary kinetic isotope effect (k H/kD = 6.61 at 298 K). The temperature dependence of the kinetic isotope effect suggested the symmetrical transition state in the rate-determining step. The rate constants of oxidation of four vicinal diols show excellent correlation with Taft's ∑ σ* values with negative reaction constant, ρz.ast;. The rate of oxidation of ethanediol has been determined in nineteen different solvents. An analysis of the solvent effect indicates the importance of the cation-solvating power of the solvents. A suitable mechanism has been postulated involving the formation of chromate ester in a pre-equilibrium.
Oxidation of some vicinal and non-vicinal diols by tetrakis(pyridine)silver dichromate: A kinetic and mechanistic study
Meena,Daiya,Sharma,Banerji,Kotai,Sharma, Vinita
experimental part, p. 1887 - 1893 (2012/04/04)
The kinetics of oxidation of four vicinal, four non-vicinal diols and two of their monoethers by tetrakis(pyridine)-silver dichromate (TPSD) have been studied in dimethylsulphoxide (DMSO). The main product of oxidation is the corresponding hydroxycarbonyl compound. The reaction is first order in TPSD. Michaelis-Menten type of kinetics is observed with respect to the diols. The reaction is catalysed by hydrogen ions. The hydrogen ion dependence has the form : kobs = a + b (H+]. The oxidation of [1,1,2,2- 2H4] ethanediol exhibits a substantial primary kinetic isotope effect (kH/kD = 5.91 at 298 K). The reaction has been studied in nineteen different organic solvents and the solvent effect has been analysed using Taft's and Swain's multiparametric equations. The temperature dependence of the kinetic isotope effect indicates the presence of a symmetrical transition state in the rate-determining step. A suitable mechanism has been proposed.
Oxidation of some vicinal and non-vicinal diols by morpholinium chlorochromate: A kinetic and mechanistic study
Barthora,Baghmar,Agarwal,Sharma, Vinita
experimental part, p. 677 - 683 (2012/04/10)
The kinetics of oxidation of four vicinal, four non-vicinal diols and two of their monoethers by morpholinium chlorochromate (MCC) have been studied in dimethylsulphoxide (DMSO). The main product of oxidation is the corresponding hydroxycarbonyl compound. The reaction is first order in MCC and the diols. The reaction is catalysed by hydrogen ions. The hydrogen ion dependence is taking the form : kobs = a + b [H+]. The oxidation of [1,1,2,2-2H4]ethanediol exhibits a substantial primary kinetic isotope effect (kH/kD = 5.82 at 298 K). The reaction has been studied in nineteen different organic solvents and the solvent effect has been analysed using Taft's and Swain's multiparametric equations. The temperature dependence of the kinetic isotope effect indicates the presence of a symmetrical transition state in the rate-determining step. A suitable mechanism has been proposed.
A convenient and effective method for the regioselective deuteration of alcohols
Maegawa, Tomohiro,Fujiwara, Yuta,Inagaki, Yuya,Monguchi, Yasunari,Sajiki, Hironao
supporting information; experimental part, p. 2215 - 2218 (2009/10/02)
The convenient and regioselective deuteration of hydroxy groups on vicinal carbons was achieved by the combination of 5% ruthenium on carbon (Ru/C), hydrogen gas and deuterium oxide (D2O).
New deuterated oligo(ethylene glycol) building blocks and their use in the preparation of surface active lipids possessing labeled hydrophilic tethers
Faragher, Robert J.,Schwan, Adrian L.
, p. 1371 - 1378 (2008/04/12)
(Chemical Equation Presented) For the introduction of additional analysis protocols of tethered molecules, a method is presented to prepare functionalized, deuterated oligo(ethylene glycols) from ethylene glycol-d 4. Partial oligomerization of ethylene glycol-d4 and conversion to ditosylates is accompanied by coupling reactions to prepare doubly benzyl protected oligo(ethylene glycols) with two to five repeating units. The tetramer bearing 16 deuteria was elaborated at both ends to eventually prepare 2,3-di-O-phytanyl-sn-glycerol-1-tetraethylene glycol-D,L-α-lipoic acid ester (DPTL), which bears a fully deuterated tetra(ethylene glycol) spacer group. Through linking of functionalized components, an analogue of DPTL possessing an octa(ethylene glycol) spacer group was prepared, both in deuterated and unlabeled form.
