A new strategy for the stereoselective synthesis of unnatural α-amino acids

A new method for the synthesis of racemic non-proteinogenic α-amino acids has been developed, which involves (i) hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron rich alkenes such as enol ethers, enamines and allylsilanes, (ii) NaCNBH₃ reduction of the CN bond in the oxazines thus generated, the stereochemistry of the products being controlled by epimerisation of the thermodynamically less stable isomer to the more stable one, (iii) protection of the N-H group as N-Boc and (iv) finally, N-O bond cleavage of both free and protected products to give proline or bis-homoserine derivatives, respectively. An example with concomitant reduction of the carboxylate group, resulting in the formation of the respective amino alcohol is reported. Applying this methodology to a homochiral enol ether, the protected parent d-proline was prepared in enantiomerically pure form, whereas the asymmetric synthesis of the respective bis-homoserine was unsuccessful.     

Studies in sigmatropic rearrangements of N-prenylindole derivatives--a formal enantiomerically pure synthesis of tryprostatin B

Rearrangement of N(a)-prenyl-N(b)-acetyltryptamine, induced by BF3.Et2O at low temperature, leads to a 2-prenyl derivative, and thence to the tricyclic tryptamine 7 and the indoline 8. Similarly, N(a)-prenyl-N(b)-phthaloyl-l-tryptophan methyl ester furnished the corresponding 2-prenyl derivative 16, a known advanced precursor of tryprostatin B. Density functional (B3LYP) calculations for the putative rearrangement transition state for N-prenylskatole show that prior coordination of BF3 to the indolic nitrogen changes the character of the subsequent sigmatropic pericyclic shifts from being entirely covalent to acquiring a significant degree of ionic character. The shifting prenyl group favours the endo over the exo mode of the transition state by 4.1 kcal mol(-1).     

An empirical process for the design of high-throughput screening deck filters

A process for objective identification and filtering of undesirable compounds that contribute to high-throughput screening (HTS) deck promiscuity is described. Two methods of mapping hit promiscuity have been developed linking SMARTS-based structural queries with historical primary HTS data. The first compares an expected assay hit rate to actual hit rates. The second examines the propensity of an individual compound to hit multiple assays. Statistical evaluation of the data indicates a correlation between the resultant functional group filters and compound promiscuity. These data corroborate a number of commonly applied filters as well as producing some unexpected results. Application of these models to HTS collection triage reduced the number of in-house compounds considered for screening by 12%. The implications of these findings are further discussed in the context of the HTS screening set and combinatorial library design as well as compound acquisition.     

Catalytic properties of the dioxomolybdenum siloxide MoO2(OSiPh3)2 and its 2,2'-bipyridine adduct MoO2(OSiPh3)2(bpy)

The tetrahedral triphenylsiloxy complex MoO(2)(OSiPh(3))(2) (1) and its Lewis base adduct with 2,2'-bipyridine, MoO(2)(OSiPh(3))(2)(bpy) (2), were prepared and characterised by IR/Raman spectroscopy, and thermogravimetric analysis. Both compounds catalyse the epoxidation of cis-cyclooctene at 55 degrees C using tert-butylhydroperoxide (t-BuOOH) is decane as the oxidant, giving 1,2-epoxycyclooctane as the only product. The best results were obtained in the absence of a co-solvent (other than the decane) or in the presence of 1,2-dichloroethane, while much lower activities were obtained when hexane or acetonitrile were added. With no co-solvent, catalyst 1 (initial activity 272 mol x molMo(-1) x h(-1)for a catalyst:substrate: oxidant molar ratio of 1:100:150) is much more active than 2(initial activity 12 mol x molMo(-1) x h(-1)). The initial reaction rates showed first order dependence with respect to the initial concentration of olefin. With respect to the initial amount of oxidant, the rate order dependence for 1 (1.9) was higher than that for 2 (1.6).The dependence of the initial reaction rate on reaction temperature and initial amount of catalyst was also studied for both catalysts. The lower apparent activation energy of 1 (11 kcal x mol(-1)) as compared with 2 (20 kcal x mol(-1)) is in accordance with the higher activity of the former.     

Explaining the visible and near-infrared circular dichroism spectra of light-harvesting 1 complexes from purple bacteria: a modeling study

In this work, we investigate the origin and characteristics of the circular dichroism (CD) spectrum of various light-harvesting 1 (LH1) complexes. The near-infrared (NIR) CD signal of these core antennae is strongly nonconservative, and the nature of this nonconservativity is under examination in this paper. So far, on the basis of the high-resolution structures of LH2, we have been able to model the absorption and CD spectra in the bacteriochlorophyll (BChl) Q(Y) and Q(X) regions of LH2 (Georgakopoulou et al., Biophys. J. 2002, 82, 2184-2197), as well as in the carotenoid region (Georgakopoulou et al., Biophys. J. 2004, 87, 3010-3022). We proceed by applying the same modeling method in order to reproduce the LH1 spectra. We assume a ring of dimers in a perfect circular arrangement with 16-fold symmetry, and account for all excitonic interactions within the ring. Because LH1 complexes exhibit Q(Y) and Q(X) CD signals of very low intensity, higher transitions can easily affect these regions. Therefore, we expand the model and take into account also the Soret and carotenoid transitions. We can now understand the shape of the absorption and CD spectra and contemplate the structure of the LH1 complex. The latter is similar to LH2 in that it is a very symmetric ring dominated by excitonic interactions. The larger number of symmetry and the bigger diameter of LH1, combined with small rotations of the BChl transition dipole moments, are responsible for the display of CD signals that are very low in intensity. The interaction of the Q(Y) with the carotenoid transitions results in complete loss of the conservativity. Interaction energies between all the pigments in the ring are calculated, and their values are in good accordance with what is reported in the literature.     

A Categorical Structure for the Virtual Braid Group

This article gives a new interpretation of the virtual braid group in terms of a strict monoidal category SC that is freely generated by one object and three morphisms, two of the morphisms corresponding to basic pure virtual braids and one morphism corresponding to a transposition in the symmetric group. This point of view makes many relationships between the virtual braid group and the pure virtual braid group apparent, and makes representations of the virtual braid groups and pure virtual braid groups via solutions to the algebraic Yang–Baxter Equation equally transparent. In this categorical framework, the virtual braid group has nothing to do with the plane and nothing to do with virtual crossings. It is a natural group associated with the structure of algebraic braiding.     

Study of carrier concentration profiles in Al‐implanted Ge by micro‐Raman spectroscopy under different excitation wavelengths

The distribution profile of Al implanted in crystalline Ge has been investigated by micro‐Raman spectroscopy. Using different excitation laser lines, corresponding to different optical penetration depths, the Al concentration at different depths beneath the sample surface has been studied. We have found a strong correlation between the intensity of the Al–Ge Raman peak at ~370 cm⁻¹, which is due to the local vibrational mode of substitutional Al atoms, and the carrier concentration profile, obtained by the spreading resistance profiling analysis. A similar connection has been also observed for both shape and position of the Ge–Ge Raman peak at ~300 cm⁻¹. According to these experimental findings, we propose here a fast and nondestructive method, based on micro‐Raman spectroscopy under different excitation wavelengths, to estimate the carrier concentration profiles in Al‐implanted Ge. Copyright © 2013 John Wiley & Sons, Ltd.