A short and highly stereoselective synthesis of α-(2-aminothiazolyl)-C-nucleosides

A short route to novel α-(2-aminothiazolyl)-C-nucleosides has been developed. The key step was the high diastereoselective reduction of the hemiacetal intermediates using L-Selectride, which afforded the corresponding R-diols in quantitative yields. These diols were converted, after C4-C1 ring closure and protecting groups cleavage, to their corresponding free α-C-nucleosides.     

Hétérocycles à fonction quinone. 7. Benzo[f]quinazolinediones-7,10 à action antitumorale potentielle

Few benzo[f]quinazoline-7,10-diones 4a-c are prepared by oxidation, with potassium nitrosodisulfonate, of the corresponding benzo[f]quinazolinamines, made by reduction of the nitro analogues which were obtained from 8-methoxybenzo[f]quinazolin-1(2H)-one. The compound 4a shows an interesting cytotoxicity.     

Diffusion of Myelin Oligodendrocyte Glycoprotein in Living OLN-93 Cells Investigated by Raster-Scanning Image Correlation Spectroscopy (RICS)

Many membrane proteins and lipids are partially confined in substructures ranging from tens of nanometers to micrometers in size. Evidence for heterogeneities in the membrane of oligodendrocytes, i.e. the myelin-producing cells of the central nervous system, is almost exclusively based on detergent methods. However, as application of detergents can alter the membrane phase behaviour, it is important to investigate membrane heterogeneities in living cells. Here, we report on the first investigations of the diffusion behavior of the myelin-specific protein MOG (myelin oligodendrocyte glycoprotein) in OLN-93 as studied by the recently developed RICS (raster-scanning image correlation spectroscopy) technique. We implemented RICS on a standard confocal laser-scanning microscope with one-photon excitation and analog detection. Measurements on FITC-dextran were used to evaluate the performance of the system and the data analysis procedure. Ellen Gielen and Nick Smisdom contributed equally to this work.     

NMR analysis of a Tau phosphorylation pattern

The phosphorylation of the neuronal Tau protein modulates both its physiological role of microtubule binding and its aggregation into paired helical fragments observed in Alzheimer's diseased neurons. However, detailed knowledge of the role of phosphorylation at specific sites has been hampered by the analytical difficulties to evaluate the level of site-specific phosphate incorporation. Even with recombinant kinases, mass spectrometry and immunodetection are not evident for determining the full phosphorylation pattern in a qualitative and quantitative manner. We show here that heteronuclear NMR spectroscopy on a 15N labeled Tau sample modified by the cAMP dependent kinase allows identification of all phosphorylation sites, measures their level of phosphate integration, and yields kinetic data for the enzymatic modification of the individual sites. Filtering through the 15N label discards the necessity of any further sample purification and allows the in situ monitoring of kinase activity at selected sites. We finally demonstrate that the NMR approach can equally be used to evaluate potential kinase inhibitors in a straightforward manner.     

First total synthesis of (−)-8-epi-9-deoxygoniopypyrone

The structure and absolute configuration of natural 8-epi-9-deoxygoniopypyrone have been confirmed by an efficient and highly diastereoselective synthesis in 15 steps from (S)-mandelic acid with an overall yield of 43%.     

Mathematical justification of a nonlinear integro-differential equation for the propagation of spherical flamesJustification mathématique d'une équation intégro-différentielle non linéaire pour un modèle de flamme sphérique

This Note is devoted to the justification of an asymptotic model for quasisteady three-dimensional spherical flames proposed by G. Joulin [7]. The paper [7] derives, by means of a three-scale matched asymptotic expansion, starting from the classical thermo-diffusive model with high activation energies, an integro-differential equation for the flame radius. In the derivation, it is essential for the Lewis number – i.e., the ratio between thermal and molecular diffusion – to be strictly less than unity. In this Note, we give the main ideas of a rigorous proof of the validity of this model, under the additional restriction that the Lewis number is close to 1. To cite this article: C. Lederman et al., C. R. Acad. Sci. Paris, Ser. I 334 (2002) 569–574.     

Les formes de torsion holomorphes du complexe de de RhamThe holomorphic torsion forms of the de Rham complex

In this Note, we announce the vanishing of the holomorphic torsion forms of the relative de Rham complex of an equivariant fibration. To cite this article: J.-M. Bismut, C. R. Acad. Sci. Paris, Ser. I 335 (2002) 243–247.     

Stereospecific Synthesis of 2-Oxazinyl-4-oxoazetidinecarbamates Starting from a 1,2-Diazepine. A new type of intramolecular transbenzoylation

Azeitidinodiazepines 4b and 4c react with acylnitroso dienophiles 5a–c , specifically from their convexe α-side, but in a non-regiospecific way, leading thereby stereospecifically to the expected adducts 6a–d and 7a–d . The three-dimensional structures of 6a and 7a were determined by X-ray analyses which corroborated their NMR data. OsO₄ cis-glycolization occurred in good yield with the inverse adducts 7a and 7e and led to the rearranged products 10 . These latter ones result from an intramolecular N- to O-transbenzoylation of the short-lived intermediates 9 followed by fragmentation of the animal function. X-Ray analysis of 7a showed the N(10) atom to be pyramidal, a result which demonstrates that it does not have any pronounced benzamide character; otherwise no such N- to O-transbenzoylation would have taken place. Structure and relative configuration of 10a were ascertained by X-ray analysis which confirmed its NMR data as well as the stereochemical outcome of its formation.     

Electrochemistry of vitamin B12: Part VII. Role of the base-off/base-on reaction in the oxido-reduction in the B12r-B12s couple in non-aqueous solvents

The cyclic voltammetric study of vitamin B_12r in DMSO shows the importance of the base-on/base-off reaction in the electrochemical reduction mechanism. Depending upon the flux of electrons flowing through the system. part of the base-on complex is reduced through prior opening of the nucleotide side-chain which gives rise to the more easily reduced DMSO-Co(II) complex. The quantitative analysis of the variations of the peak heights with the sweep rate allows the thermodynamic and kinetic characterization of the base-on/base-off reactions to be determined. DMSO thus appears as a stronger ligand toward Co(II) than water, leading to an increased participation of the base-off complex in the reduction process. The greater stability of the DMSO complex is also related to the observation that electron transfer is significantly slower than in the case of the water complex. The importance of the ligand exchange reactions in the reduction of B_12r is confirmed by the effect of pyridine additions. Three complexes then participate in the reduction process, their reduction potentials lying in the order DMSO >Py >Bzm. The reduction mechanism involving the interconversion of the three complexes is described as a function of the electrode potential, the flux of electrons and the pyridine concentration. An estimation of the equilibrium and rate constants of the three ligand exchange reactions is made, based on the variations of the cyclic voltammograms with the sweep rate and the pyridine concentration.     

NMR (195Pt and 13C) contribution to the study of some Pt(II), Pt(IV) and mixed-valence thioamido complexes

The ¹⁹⁵Pt and ¹³C chemical shifts (δ_Pt and δ_c) are reported for platinum(II), platinum(IV) and class II mixed-valence complexes, with general formula [PtL₄]X₂, cis- and trans-PtL₂X₂, PtL₂X₄ and Pt₂L₄X₆ (where L may be thiourea, 2-imidazolidine-thione, tetrahydro 2-pyrimidinethione, thiocaprolactam, pyridine-2-thione and tetramethylthiourea, and X may be Cl or Br). The ¹⁹⁵Pt chemical shifts can be understood in view of ¹³C data in terms of variations of electronegativities and σ-donor abilities of ligands attached to platinum.