Synthesis of 5‐N‐glycosylaminopyrimidines. A new class of compounds with potential anti‐aids activity

Reactions between 5,6‐diaminopyrimidines 1a‐c and pentoses 2a‐e yield 5‐N‐glycosylaminopyrirnidines or 7‐polyhydroxyalkylpteridines, depending on the presence or absence of acetic acid. The “in vitro” anti‐HIV activity of 6‐amino‐2‐methoxy‐3‐methyl‐5‐N‐D‐ribosylaminopyrimidin‐4(3H)‐one 3e, 6‐amino‐2‐methoxy‐3‐methyl‐5‐N‐β‐D‐xylopyranosylaminopyrimidin‐4(3H‐one 3f, and 6‐amino‐2‐methylthio‐5‐N‐β‐L‐xylopyranosylminopyrimidin‐4(3H)‐one 3k, appears to be promising.     

Weighted Inequalities for Schrödinger Type Singular Integrals

Journal of Fourier Analysis and Applications - Related to the Schrödinger operator $$L=-Delta +V$$ , the behaviour on $$L^p$$ of several first and second order Riesz transforms was studied by...     

Competition between reaction and intramolecular energy redistribution in solution: observation and nature of nonstatistical dynamics in the ozonolysis of vinyl ethers

Experimental product ratios in ozonolyses of alkyl vinyl ethers in solution do not fit with expectations based on statistical rate theories. The selectivity among cleavage pathways increases with the size of the alkyl group but to an extent that is far less than RRKM theory would predict. Trajectory studies account for the observed selectivities and support a mechanism involving a competition between cleavage of the primary ozonide and intramolecular vibrational energy redistribution. A statistical model is presented that assumes that RRKM theory holds for a molecular subset of the primary ozonides, allowing the rates of energy loss from the ozonides to be estimated from the observed product ratios.     

A computational study of the thermolysis of β‐hydroxy ketones in gas phase and in m‐xylene solution

Theoretical calculations at the M05‐2X/6‐31+G(d) level of theory have been carried out in order to explore the nature of the mechanism of the thermal decomposition reactions of the β‐hydroxy ketones, 4‐hydroxy‐2‐butanone, 4‐hydroxy‐2‐pentanone, and 4‐hydroxy‐2‐methyl‐2‐pentanone in gas phase and in m‐xylene solution. The mechanism proposed is a one‐step process proceeding through a six‐membered cyclic transition state. A reasonable agreement between experimental and calculated activation parameters and rate constants has been obtained, the tertiary : secondary : primary alcohol rate constant ratio being calculated, at T = 503.15 K, as 5.9:4.7:1.0 in m‐xylene solution and 44.1:5.0:1.0 in the gas phase, compared with the experimental values, 3.7:1.3:1.0 and 13.5:3.2:1.0, respectively. The progress of the thermal decomposition reactions of β‐hydroxy ketones has been followed by means of the Wiberg bond indices. The lengthening of the O₁–C₂ bond with the initial migration of the H₆ atom from O₅ to O₁ can be seen as the driving force for the studied reactions. Calculated synchronicity values indicate that the mechanisms correspond to concerted and highly synchronous processes. The transition states are “advanced”, nearer to the products than to the reactants. Copyright © 2012 John Wiley & Sons, Ltd.     

Thermal decomposition of 4‐hydroxy‐2‐butanone in m‐xylene solution: Experimental and computational study

The mechanism of thermal decomposition of 4‐hydroxy‐2‐butanone in m‐xylene solution was studied experimentally and theoretically at the M05‐2X/6‐31G(d, p) level of theory. It follows first‐order kinetics and appears to be homogeneous and unimolecular. The proposed mechanism is via a six‐membered cyclic transition state to give a mixture of formaldehyde and acetone. Rate constant values were experimentally determined at three temperatures: 483.15, 493.15, and 503.15 K. Calculated rate constants are of the same order of magnitude than the experimental ones. Calculated Gibbs energies of activation agree very well with the experimental values. Computationally, the progress of the reactions was followed by means of the Wiberg bond index. The results indicate that the transition state has an intermediate character between reactants and products, and the calculated synchronicity shows that the reaction is slightly asynchronous. The bond‐breaking processes are more advanced than the bond‐forming ones, indicating a bond deficiency in the transition state. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 407–413, 2012     

Synthesis and Characterization of a Hypoxia‐Sensitive MRI Probe

Tissue hypoxia occurs in pathologic conditions, such as cancer, ischemic heart disease and stroke when oxygen demand is greater than oxygen supply. An imaging method that can differentiate hypoxic versus normoxic tissue could have an immediate impact on therapy choices. In this work, the gadolinium(III) complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) with a 2‐nitroimidazole attached to one carboxyl group via an amide linkage was prepared, characterized and tested as a hypoxia‐sensitive MRI agent. A control complex, Gd(DO3A‐monobutylamide), was also prepared in order to test whether the nitroimidazole side‐chain alters either the water proton T₁ relaxivity or the thermodynamic stability of the complex. The stabilities of these complexes were lower than that of Gd(DOTA)^? as expected for mono‐amide derivatives. The water proton T₁ relaxivity (r₁), bound water residence lifetime (τ_M) and rotational correlation time (τ_R) of both complexes was determined by relaxivity measurements, variable temperature ¹⁷O NMR spectroscopy and proton nuclear magnetic relaxation dispersion (NMRD) studies. The resulting parameters (r₁=6.38 mM ^?1 s^?1 at 20 MHz , τ_M=0.71 μs, τ_R=141 ps) determined for the nitroimidazole derivative closely parallel to those of other Gd(DO3A‐monoamide) complexes of similar molecular size. In vitro MR imaging experiments with 9L rat glioma cells maintained under nitrogen (hypoxic) versus oxygen (normoxic) gas showed that both agents enter cells but only the nitroimidazole derivative was trapped in cells maintained under N₂ as evidenced by an approximately twofold decrease in T₁ measured for hypoxic cells versus normoxic cells exposed to this agent. These results suggest that the nitroimidazole derivative might serve as a molecular reporter for discriminating hypoxic versus normoxic tissues by MRI.     

Determination of selenium species in human urine by high performance liquid chromatography and inductively coupled plasma mass spectrometry

A method developed to determine organic and inorganic selenium species in human urine samples is presented in detail. After a simple sample treatment based on elimination of non-charged organic compounds, selenium species were separated by high performance liquid chromatography (HPLC) on a Spherisorb 5 ODS/AMINO column using two different chromatographic conditions: phosphate buffers at pH 2.8 and 6.0. Detection was carried out using an on-line inductively coupled plasma mass spectrometer (ICP-MS). Trimethylselenonium ion and two unknown selenium species in urine samples were found. Selenium species were shown to have stability problems, with the maximum allowed storage time of 1 week.     

Reaction of 6-glycopyranosylaminopyrimidin-4-ones with malonic acids. Synthesis of 8-glycopyranosylpyrido[2,3-d]pyrimidin-4-one derivatives

Summary Reactions of 6-glycopyranosylaminopyrimidin-4-ones1 a–d with malonic, methyl malonic and ethyl malonic acids are discussed in this paper. These reactions have been carried out in acetic anhydride at 100°C affording the 8-glycopyranosylpyrido[2,3-d]pyrimidin-4-ones2 a–d,3 c–d and the 5-acyl-6-glycopyranosylaminopyrimidin-6-ones4 a–d,5 a–d.

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Reaktion von 6-Glycopyranosylaminopyrimidin-4-onen mit Malonsäuren. Synthese von 8-Glycopyranosylpyrido[2,3-d]pyrimidin-4-on-Dervaten

Zusammenfassung Es werden Reaktionen der 6-Glycopyranosylaminopyrimidin-4-one1 a–d mit Malonsäure, Methylmalonsäure und Ethylmalonsäure diskutiert. Die Reaktionen wurden in Essigsäureanhydrid bei 100°C ausgeführt und ergaben 8-Glycopyranosylpyrido[2,3-d]pyrimidin-4-one2 a–d,3 c–d und die 5-Acyl-6-glycopyranosylaminopyrimidin-6-one4 a–d und5 a–d.