Preparation of conformationally restricted β2,2- and β2,2,3-amino esters and derivatives containing an all-carbon quaternary center

Abstract: β-Amino acids are routinely incorporated into peptidic drugs to increase their stability and to incur conformational biases. However, the synthesis of highly substituted β-amino acids still represents a great challenge. A new approach to their preparation is reported involving a Vilsmeier–Haack reaction with nonaromatic carbon nucleophiles. The highly challenging preparation of contiguous tertiary and all-carbon quaternary centers was successfully used to generate several β2,2,3-amino esters, such as derivatives of homoproline, homoalanine, and homopipecolinic esters

Génération de centres quaternaires complètement carbonés par réaction Vilsmeier-Haack intermoléculaire : application à la synthèse d'acides beta-animés et dérivés

Les travaux présentés dans ce mémoire ont été effectués dans le but de développer une nouvelle méthodologie mettant en oeuvre une réaction de Vilsmeier-Haack intermoléculaire afin d'accéder à differents composes ?-aminés contenant un centre quaternaire carboné. Le premier chapitre portera sur la mise en place d'une version racémique et non catalytique de cette nouvelle méthodologie. Les synthèses des esters ?-2,2 -aminés, des alcools ? 2,2 et ?2,2,3 -aminés et des esters ? 2,2,3 -aminés seront présentées. De plus, il sera également question de la saponification et de la déprotection de certains de ces composés afin d'obtenir les acides ?-aminés et les esters-?-aminés libres correspondants. Le deuxième chapitre mettra en lumière les travaux effectués dans le but de développer une version asymétrique non catalytique de cette même réaction. L'un des premiers objectifs étant la formation d'un ion iminium chiral, l'attention sera mise sur les moyens pour y parvenir, soit la substitution d'un triflyliminium et l'activation directe d'un amide par un auxiliaire chiral. Dans le premier cas, i1 sera question d'oxydes métalliques et dans le deuxieme, de metaux reliés à un groupement partant. Le troisième chapitre consistera seulement à la mise en place d'une éventuelle réaction asymétrique catalytique. Les restrictions, lesquelles dépendront du moyen pris pour former l'ion iminium chiral, seront présentées sous forme de cycle catalytique. [symboles non conformes

Layer-resolved imaging of domain wall interactions in magnetic tunnel junction-like trilayers

We have performed a layer-resolved, microscopic study of interactions between domain walls in two magnetic layers separated by a non-magnetic one, using high-resolution x-ray photoemission electron microscopy. Domain walls in the hard magnetic Co layer of a Co/Al2O3/FeNi trilayer with in-plane uniaxial anisotropy strongly modify the local magnetization direction in the soft magnetic FeNi layer. The stray fields associated to the domain walls lead to an antiparallel coupling between the local Co and FeNi moments. For domain walls parallel to the easy magnetization axis this interaction is limited to the domain wall region itself. For strongly charged (head-on or tail-to-tail) walls, the antiparallel coupling dominates the interaction over radial distances up to several micrometers from the centre of the domain wall.Comment: Published version, J. Phys.: Condens. Matter 19, 476204 (2007

Influence of topography and Co domain walls on the magnetization reversal of the FeNi layer in FeNi/Al_2\_2O_3\_3/Co magnetic tunnel junctions

We have studied the magnetization reversal dynamics of FeNi/Al$\_2$O$\_3$/Co magnetic tunnel junctions deposited on step-bunched Si substrates using magneto-optical Kerr effect and time-resolved x-ray photoelectron emission microscopy combined with x-ray magnetic circular dichroism (XMCD-PEEM). Different reversal mechanisms have been found depending on the substrate miscut angle. Larger terraces (smaller miscut angles) lead to a higher nucleation density and stronger domain wall pinning. The width of domain walls with respect to the size of the terraces seems to play an important role in the reversal. We used the element selectivity of XMCD-PEEM to reveal the strong influence of the stray field of domain walls in the hard magnetic layer on the magnetic switching of the soft magnetic layer.Comment: 8 Pages, 7 Figure

Dynamics of magnetic domain wall motion after nucleation: Dependence on the wall energy

The dynamics of magnetic domain wall motion in the FeNi layer of a FeNi/Al2O3/Co trilayer has been investigated by a combination of x-ray magnetic circular dichroism, photoelectron emission microscopy, and a stroboscopic pump-probe technique. The nucleation of domains and subsequent expansion by domain wall motion in the FeNi layer during nanosecond-long magnetic field pulses was observed in the viscous regime up to the Walker limit field. We attribute an observed delay of domain expansion to the influence of the domain wall energy that acts against the domain expansion and that plays an important role when domains are small.Comment: Accepted for publication in Physical Review Letter

Publications numériques scientifiques universitaires internationales : Disruption, quels acteurs, quels projets ?

Mémoire du master 2 PUN portant sur le phénomène de disruption dans les publications scientifiques

Arterial age as a substitute for chronological age in the AGLA risk function could improve coronary risk prediction

PRINCIPLES: As a result of the relatively low sensitivity of coronary risk charts, such as the Swiss coronary risk calculator (Arbeitsgruppe Lipide und Atherosklerose, AGLA), for detecting subjects with future myocardial infarction, the performance of arterial age (aa) as a surrogate marker for chronological age (ca) was tested. METHODS: In a practice based sample, burden of carotid plaque was obtained with ultrasound, using total plaque area (TPA). In this derivation cohort, sex-specific 5-year groups of mean TPA were calculated in subjects aged between 35 and 79 years. The arterial age formula was found by fitting an exponential function on these data. AGLAca and AGLAaa were tested externally for their ability to detect 13 myocardial infarctions in 684 subjects (validation cohort). RESULTS: The derivation cohort included 1,500 subjects (mean age 59 ± 9 years, mean TPA 54 ± 52 mm2, 5% diabetics, 43% women). Arterial age was found to be y = 5.4175e0.0426x in men and y = 4.1942e0.0392x in women. Mean 10-year AGLAca coronary risk was comparable to AGLAaa (8% ± 9% vs 9% ± 15%). Receiver operating characteristic (ROC) analysis of AGLAca and AGLAaa results showed areas under the curve of 0.65 (p = 0.041) and 0.78 (p \u3c0.0001), respectively, (p = 0.041 for the difference = 0.13). This finding was also confirmed by a Cox proportional hazards regression model on patients\u27 event-free survival (p = not significant for AGLAca, p = 0.0003 for AGLAaa). CONCLUSIONS: Arterial age derived from TPA could be used instead of chronological age in the AGLA coronary risk function. Further studies on the external validity and cost effectiveness of the additional ultrasound imaging study are necessary