Synthesis and biological evaluation of nucleosides containing 8-amino-imidazo[1,2-α]pyrazine as an isosteric replacement for adenine

A number of novel C-nucleosides related to purine derivatives are described in which the purine moiety has been replaced by the isosteric heterocycle, 8-aminoimidazo[1,2-α]pyrazine. The nucleosides prepared include the ribo, 3′-deoxy, 2′,3′-dideoxy, and 2′,3′-unsaturated derivatives. These C-nucleosides represent derivatives containing acid stable glycosyl bonds and they can be considered as analogs of adenine- or 3-deazaade-nine-containing nucleosides. Preparation of the parent ribonucleoside was accomplished by reaction of the C-l functionalized sugar, (2ξ)-1-amino-3,6-anhydro-l-deoxy-4,5-O-isopropylidene-7-O-trityl-D-allo-heptitol with 2,3-dichloropyrazine, followed by ring closure to the 8-chloroimidazo[1,2-α]pyrazine nucleoside, conversion to the 8-amino derivative and deblocking. A single crystal X-ray structure of the parent 8-amino-3-(β-D-ribofuranosyl)imidazo[1,2-α]pyrazine is described and the conformation compared to that of formycin. The sugar-modified analogs were prepared by subsequent functional group manipulations on the sugar moiety. Biological evaluation against HIV in H9 T-lymphoid cell culture showed the nucleosides to be devoid of significant antiviral activity compared to DDA. The 3-deazaadenosine analog also demonstrated weak suppression of mouse splenic NK activity toward YAC cells (mouse lymphoma cell targets). The imidazo[1,2-α]pyrazine analog of 3-deazaadenosine showed antiinflammatory activity in vivo in the rat pleurisy carrageenan model in the same range with 3-deazaadenosine.     

Mechanisms of Cobalt/Phosphine-Catalyzed Cross-Coupling Reactions

>The combination of CoCl₂ with bidentate phosphines is known to catalyze challenging cross-coupling and Heck-type reactions, but the mechanisms of these valuable transformations have not been established. Here, we use electrospray-ionization mass spectrometry to intercept the species formed in these reactions. Our results indicate that a sequence of transmetalation, reductive elimination, and redox disproportionation convert the cobalt(II) precatalyst into low-valent cobalt complexes. These species readily transfer single electrons to alkyl bromides, which thereupon dissociate into alkyl radicals and Br⁻. In cross-coupling reactions, the alkyl radicals add to the cobalt catalyst to form observable heteroleptic complexes, which release the coupling products through reductive eliminations. In the Heck-type reactions, the low abundance of newly formed ionic species renders the analysis more difficult. Nonetheless, our results also point to the occurrence of single-electron transfer processes and the involvement of radicals in these transformations.     

A tilted rotatory frame method for the measurement of nuclear spin diffusion coefficients in solids doped with paramagnetic centers: Mn-Doped CaF<Subscript>2</Subscript>

Nuclear magnetic resonance (NMR) experiments recording the recovery of the magnetization of the nuclei in one phase, following the excitation of the nuclei in the other phase, is a classical way of studying blends inhomogeneous at the nanometer scale. Interpretation of the time recovery in terms of the spatial dimension requires knowledge of the two-phase spin diffusion coefficientsD ₀. A new method of measurement of_{D 0} is proposed on the basis of variable angle-tilted rotatory frame relaxation in homogeneous samples doped with paramagnetic centers. The choice of the tilt angle allows one to finely balance the direct relaxation by the paramagnetic center and the spin diffusion. The shape of the relaxation is analyzed with the solution for the diffusion-limited regimeM(t)/M(0)=exp[?(r ₂ t)^1/2?r ₁ t] andD ₀ then calculated fromr ₁,r ₂ and the concentration of paramagnetic centers. Conditions where reliable results can be obtained both theoretically and numerically are explored. The method has been implemented and applied to polycrystalline Mn-doped CaF₂ leading toD ₀=540±60 nm²/s, in agreement with existing values on this model compound.     

Omega- and Omega+ production in central Pb + Pb collisions at 40 and 158A GeV

Results are presented on Omega production in central Pb+Pb collisions at 40 and 158A GeV beam energy. For the first time in heavy ion reactions, rapidity distributions and total yields were measured for the sum Omega(-) + Omega(+) at 40A GeV and for Omega(-) and Omega(+) separately at 158A GeV. The yields are strongly underpredicted by the string-hadronic UrQMD model but agree better with predictions from hadron gas models.     

Diffusion after chain fragmentation in the glassy state: A SANS study

A new method to measure the extremely slow chain diffusion in polymer systems at and below the glass transition temperature is proposed. It requires polymers that can be fragmented in a well-defined manner in the glassy state. The idea is first to split all chains, while their conformations are frozen in, and then to measure at some higher temperature the diffusion of the chain fragments by small-angle neutron scattering. The structure factor changes in the course of the fragment diffusion from that of the initial long chains to that of the uncorrelated fragments. Preliminary results from experiments on blends of thermosensitive copolycarbonates and tetramethylpolycarbonate are presented. They demonstrate the viability of the technique.     

1H NMR studies of molecular relaxations of poly-1-butene

The temperature dependance of the proton NMR line shape, T₁ and T_1ρ of isotactic poly-1-butene forms I, I′, II, and III have been studied between 100 and 400 K (up to melting). The usual line shape decompositions concerning rigid vs. crystalline and mobile vs. amorphous phases are discussed. The rigid-lattice second moments were calculated introducing a fast rotation of the methyl group. Complex spin-lattice decays were analyzed as a continuous distribution of rates. Relaxation behavior was analyzed in terms of a Williams-Watt correlation function. Motions in the crystalline parts of samples in forms II and III very similar to the amorphous one were revealed, leading us to compare form II to a condis crystal during the crystal form transformation. © 1995 John Wiley & Sons, Inc.     

Plastic deformation of poly(tetramethylene oxide). II. Molecular orientation as measured by x-ray diffraction and NMR measurements

The orientation of the crystalline and amorphous phases in uniaxially drawn samples of polytetramethylene oxide has been studied by x-ray and NMR methods. Pole figure measurements give the orientation of the crystalline phase. Its dependence on the draw ratio does not obey the pseudoaffine model. The crystalline fraction is derived from NMR measurements at temperatures between T_g and T_m, where the free induction decay (FID) of the unoriented sample can be analyzed in terms of a rigid (crystalline), a constrained, and an amorphous phase. Low temperature (T < T_g) measurements of the NMR second-moment anisotropy in protonated and deuterated samples give a mean orientation of the chains higher than that corresponding to the crystalline phase. The lack of anisotropy in the tail of the FID at temperatures between T_g and T_m indicates no appreciable anisotropy in the truly amorphous interlamellar phase. From this and from the ratio of the P₄/P₂ orientations, factors which obey the “most probable distribution,” it is concluded that the amorphous orientation is due to the layer of constrained chains at the surface of the lamellae.     

Molecular orientation in stretched poly(vinyl alcohol). I. NMR anisotropy and birefringence

The second and fourth moments of the proton resonance line in stretched poly(vinyl alcohol) samples have been measured by a pulse technique. Their anisotropy has been analyzed at different elongation ratios λ. The use of the second and fourth moments gives an interesting cross-check on the reliability of the results. Despite the fact that the lattice sums required for absolute determination of the orientation cannot be calculated, coefficients related to the second and fourth moments of the orientation distribution function can be compared to the prediction of the quasiaffine orientation scheme for the crystalline phase and to the experimental values of the birefringence as a function of λ. It is shown that NMR clearly detects the onset of the orientation of the amorphous chains above λ ≈ 4.