Diastereoselective synthesis of [alpha]-tocopherol

Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. All possess a hydrophobic side chain, which allows them to penetrate into biological membranes. Their second common feature is a chromanol moiety with a hydroxyl group that can donate a hydrogen atom. These properties make vitamin E a very important radical chain-breaking antioxidant in living organisms, and therefore also an industrial product. α-Tocopherol is the member of the vitamin E family that is preferentially absorbed and accumulated in humans. There are three stereocenters in α-tocopherol, whereas RRR-α-tocopherol (1) is the natural and biologically most active form. The R-configuration at C(2) is essential in order to be recognised by the α-tocopherol transport protein and thus maintained in the plasma. The biological activity rendered RRR-α-tocopherol (1) a synthetic target. In this work two novel syntheses of RRR-α-tocopherol (1) are presented. Both syntheses involve a highly diastereoselective epoxidation of the bis-protected phytyl hydroquinone 132 as the key step followed by a cyclisation to form the chromanol ring (figure 70). In order to find suitable stereoselective epoxidation catalysts, cyclodextrin-based catalysts were prepared and tested (figure 71). However, none of these catalysts were reactive or selective enough to be applicable to the epoxidation of bis-protected phytyl hydroquinones. However, the asymmetric Shi epoxidation proved to be a suitable epoxidation method for this purpose. A number of bis-protected phytyl hydroquinones were synthesised and subsequently epoxidised under Shi epoxidation conditions. The highest diastereoslectivity could be obtained for substrate 132. By applying Shi ketone 114, which is derived from D-fructose, epoxide 148 could be obtained with 96% de, whereas if the enantiomer ent-114 (synthesised in 5 steps from L-sorbose) was used, 147 was formed with 97% de (figure 71). The epoxide function in 148 could be selectively opened with hydride. Further transformations led to the hydroquinone 155, which could be cyclised under acidic conditions to form the chromanol ring of 1 with the desired R-configuration at C(2) (figure 72). α-Tocopherol could be synthesised in 8 steps with 93% de via this route. To the best of my knowledge, this highly diasteroselective synthesis of α-tocopherol (1) is one of the shortest in terms of numbers of steps, employing a commercially available organocatalyst. In a different approach an acid supported, “anti-Baldwin” epoxide ring opening of desilylated 147 under inversion of configuration led to the 6-membered chromanol ring. α-Tocopherol could be synthesised in 10 steps and with 93% de. This synthesis was carried out in collaboration with Julien Chapelat. To the best of our knowledge this is the second application of an organocatalyst to the construction of chromanols, having a tetrasubstituted chiral carbon centre, in high diastereoselectivity.7

Laser-Nucleus Interactions: The Quasiadiabatic Regime

The interaction between nuclei and a strong zeptosecond laser pulse with coherent MeV photons is investigated theoretically. We provide a first semi-quantitative study of the quasiadiabatic regime where the photon absorption rate is comparable to the nuclear equilibration rate. In that regime, multiple photon absorption leads to the formation of a compound nucleus in the so-far unexplored regime of excitation energies several hundred MeV above the yrast line. The temporal dynamics of the process is investigated by means of a set of master equations that account for dipole absorption, stimulated dipole emission, neutron decay and induced fission in a chain of nuclei. That set is solved numerically by means of state-of-the-art matrix exponential methods also used in nuclear fuel burnup and radioactivity transport calculations. Our quantitative estimates predict the excitation path and range of nuclei reached by neutron decay and provide relevant information for the layout of future experiments.Comment: 14 pages, 9 figures; v2 minor modifications in text, results unchange

Improving PWR core simulations by Monte Carlo uncertainty analysis and Bayesian inference

A Monte Carlo-based Bayesian inference model is applied to the prediction of reactor operation parameters of a PWR nuclear power plant. In this non-perturbative framework, high-dimensional covariance information describing the uncertainty of microscopic nuclear data is combined with measured reactor operation data in order to provide statistically sound, well founded uncertainty estimates of integral parameters, such as the boron letdown curve and the burnup-dependent reactor power distribution. The performance of this methodology is assessed in a blind test approach, where we use measurements of a given reactor cycle to improve the prediction of the subsequent cycle. As it turns out, the resulting improvement of the prediction quality is impressive. In particular, the prediction uncertainty of the boron letdown curve, which is of utmost importance for the planning of the reactor cycle length, can be reduced by one order of magnitude by including the boron concentration measurement information of the previous cycle in the analysis. Additionally, we present first results of non-perturbative nuclear-data updating and show that predictions obtained with the updated libraries are consistent with those induced by Bayesian inference applied directly to the integral observables.Comment: 10 pages, 11 figure

Photophysical Study on the Rigid Pt(II) Complex [Pt(naphen)(Cl)] (Hnaphen = Naphtho[1,2-b][1,10]Phenanthroline and Derivatives

The electrochemistry and photophysics of the Pt(II) complexes [Pt(naphen)(X)] (Hnaphen = naphtho[1,2-b][1,10]phenanthroline, X = Cl or C≡CPh) containing the rigid tridentate C^N^N-coordinating pericyclic naphen ligand was studied alongside the complexes of the tetrahydro-derivative [Pt(thnaphen)(X)] (Hthnaphen = 5,6,8,9-tetrahydro-naphtho[1,2-b][1,10]phenanthroline) and the N^C^N-coordinated complex [Pt(bdq)(Cl)] (Hbdq = benzo[1,2-h:5,4-h’]diquinoline. The cyclic voltammetry showed reversible reductions for the C^N^N complexes, with markedly fewer negative potentials (around −1.6 V vs. ferrocene) for the complexes containing the naphen ligand compared with the thnaphen derivatives (around −1.9 V). With irreversible oxidations at around +0.3 V for all of the complexes, the naphen made a difference in the electrochemical gap of about 0.3 eV (1.9 vs. 2.2 eV) compared with thnaphen. The bdq complex was completely different, with an irreversible reduction at around −2 V caused by the N^C^N coordination pattern, which lacked a good electron acceptor such as the phenanthroline unit in the C^N^N ligand naphen. Long-wavelength UV-Vis absorption bands were found around 520 to 530 nm for the C^N^N complexes with the C≡CPh coligand and were red-shifted when compared with the Cl derivatives. The N^C^N-coordinated bdq complex was markedly blue-shifted (493 nm). The steady-state photoluminescence spectra showed poorly structured emission bands peaking at around 630 nm for the two naphen complexes and 570 nm for the thnaphen derivatives. The bdq complex showed a pronounced vibrational structure and an emission maximum at 586 nm. Assuming mixed 3LC/3MLCT excited states, the vibronic progression for the N^C^N bdq complex indicated a higher LC character than assumed for the C^N^N-coordinated naphen and thnaphen complexes. The blue-shift was a result of the different N^C^N vs. C^N^N coordination. The photoluminescence lifetimes and quantum yields ΦL massively increased from solutions at 298 K (0.06 to 0.24) to glassy frozen matrices at 77 K (0.80 to 0.95). The nanosecond time-resolved study on [Pt(naphen)(Cl)] showed a phosphorescence emission signal originating from the mixed 3LC/3MLCT with an emission lifetime of around 3 µs

Magnetically-coupled piston pump for high-purity gas applications

Experiments based on noble elements such as gaseous or liquid argon or xenon utilize the ionization and scintillation properties of the target materials to detect radiation-induced recoils. A requirement for high light and charge yields is to reduce electronegative impurities well below the ppb level. To achieve this, the target material is continuously circulated in the gas phase through a purifier and returned to the detector. Additionally, the low backgrounds necessary dictate low-Rn-emanation rates from all components that contact the gas. Since commercial pumps often introduce electronegative impurities from lubricants on internal components or through small air leaks, and are not designed to meet the radiopurity requirements, custom-built pumps are an advantageous alternative. A new pump has been developed in Muenster in cooperation with the nEXO group at Stanford University and the nEXO/XENON group at Rensselaer Polytechnic Institute based on a magnetically-coupled piston in a hermetically sealed low-Rn-emanating vessel. This pump delivers high performance for noble gases, reaching more than 210 standard liters per minute (slpm) with argon and more than 170 slpm with xenon while maintaining a compression of up to 1.9 bar, demonstrating its capability for noble gas detectors and other applications requiring high standards of gas purity.Comment: 11 pages, 18 figure

The relentless variability of Mrk 421 from the TeV to the radio

The origin of the gamma-ray emission of the blazar Mrk 421 is still a matter of debate. We used 5.5 years of unbiased observing campaign data, obtained using the FACT telescope and the Fermi LAT detector at TeV and GeV energies, the longest and densest so far, together with contemporaneous multi-wavelength observations, to characterise the variability of Mrk 421 and to constrain the underlying physical mechanisms. We studied and correlated light curves obtained by ten different instruments and found two significant results. The TeV and X-ray light curves are very well correlated with a lag of <0.6 days. The GeV and radio (15 Ghz band) light curves are widely and strongly correlated. Variations of the GeV light curve lead those in the radio. Lepto-hadronic and purely hadronic models in the frame of shock acceleration predict proton acceleration or cooling timescales that are ruled out by the short variability timescales and delays observed in Mrk 421. Instead the observations match the predictions of leptonic models.Comment: 10 pages, 8 figures, 1 tabl

Contributions of the PPC to online control of visually guided reaching movements assessed with fMRI-Guided TMS

The posterior parietal cortex (PPC) plays an important role in controlling voluntary movements by continuously integrating sensory information about body state and the environment. We tested which subregions of the PPC contribute to the processing of target- and body-related visual information while reaching for an object, using a reaching paradigm with 2 types of visual perturbation: displacement of the visual target and displacement of the visual feedback about the hand position. Initially, functional magnetic resonance imaging (fMRI) was used to localize putative target areas involved in online corrections of movements in response to perturbations. The causal contribution of these areas to online correction was tested in subsequent neuronavigated transcranial magnetic stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the supramarginal gyrus for both perturbations. TMS over neighboring sites did not affect online control. Our results support the hypothesis that the aIPS is more generally involved in visually guided control of movements, independent of body effectors and nature of the visual information. Furthermore, they suggest that the human network of PPC subregions controlling goal-directed visuomotor processes extends more inferiorly than previously thought. Our results also point toward a good spatial specificity of the TMS effects. © 2010 The Author