A New Stereocontrolled Total Synthesis of the Mast Cell inhibitory Alkaloid, (+)-Monanchorin, via the Wittig Reaction of a Stabilized Ylide with a Cyclic Guanidine Hemiaminal

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An asymmetric total synthesis of the mast cell inhibitor (+)-monanchorin is reported in which a Sharpless AD on 11 and a cyclic sulfate ring opening with an azide feature as key steps. After further manipulation, a novel guanidine-controlled ester reduction provided the guanidine-hemiaminal 25 which underwent Wittig olefination to give 27. Hydrogenation and a second guanidine-controlled reduction of the ester in 28, to obtain aldehyde 29, then set up a trifluoroacetic acid mediated cyclization to give (+)-monanchorin TFA salt.

Identification of Pseudomonas aeruginosa by a duplex real-time polymerase chain reaction assay targeting the ecfX and the gyrB genes

Phenotypic identification of Gram-negative bacteria from respiratory specimens of patients with cystic fibrosis carries a high risk of misidentification. Molecular identification techniques that use single-gene targets are also susceptible to error, including cross-reaction issues with other Gram-negative organisms. In this study, we have designed a Pseudomonas aeruginosa duplex real-time polymerase chain reaction (PCR) (PAduplex) assay targeting the ecfX and the gyrB genes. The PAduplex was evaluated against a panel of 91 clinical and environmental isolates that were presumptively identified as P. aeruginosa. The results were compared with those obtained using a commercial biochemical identification kit and several other P. aeruginosa PCR assays. The results showed that the PAduplex assay is highly suitable for routine identification of P. aeruginosa isolates from clinical or environmental samples. The 2-target format provides simultaneous confirmation of P. aeruginosa identity where both the ecfX and gyrB PCR reactions are positive and may also reduce the potential for false negatives caused by sequence variation in primer or probe targets.

Application of Asymmetric Marcus-Hush Theory to Voltammetry in Room-Temperature Ionic Liquids

Asymmetric MarcusHush (AMH) theory is applied for the first time in ionic solvents to model the voltammetric reduction of oxygen in 1-butyl-1-methylpyrrolidinium bis-(trifluoromethylsulfonyl)-imide and of 2-nitrotoluene (2-NT), nitrocyclopentane (NCP), and 1-nitro-butane (BuN) in trihexyltetradecylphosphonium tris(pentafluoroethyl)trifluorophosphate on a gold microdisc electrode. An asymmetry parameter, gamma, was estimated for all systems as -0.4 for the reduction of oxygen and -0.05, 0.25, and 0 +/- 0.05 for the reductions of 2-NT, NCP, and BuN, respectively, which suggests equal force constants of reactants and products in the case of 2-NT and BuN and unequal force constants for oxygen and NCP where the force constants of the oxidized species are greater than the reduced species in the case of oxygen and less than the reduced species in the case of NCP. Previously measured values for a, the Butler-Volmer transfer coefficient, reflect this in each case. Where appreciable asymmetry occurs, AMH theory was seen to parametrize the experimental data better than either Butler-Volmer or symmetric Marcus-Hush theory, allowing additionally the extraction of reorganization energy. This is the first study to provide key physical insights into electrochemical systems in room-temperature ionic liquids using AMH theory, allowing elucidation of the reorganization energies and the relative force constants of the reactants and products in each reaction.

Three-dimensional simulations of gravitationally confined detonations compared to observations of SN 1991T

The gravitationally confined detonation (GCD) model has been proposed as a possible explosion mechanism for Type Ia supernovae in the single-degenerate evolution channel. It starts with ignition of a deflagration in a single off-centre bubble in a near-Chandrasekhar-mass white dwarf. Driven by buoyancy, the deflagration flame rises in a narrow cone towards the surface. For the most part, the main component of the flow of the expanding ashes remains radial, but upon reaching the outer, low-pressure layers of the white dwarf, an additional lateral component develops. This causes the deflagration ashes to converge again at the opposite side, where the compression heats fuel and a detonation may be launched. We first performed five three-dimensional hydrodynamic simulations of the deflagration phase in 1.4 M⊙ carbon/oxygen white dwarfs at intermediate-resolution (2563computational zones). We confirm that the closer the initial deflagration is ignited to the centre, the slower the buoyant rise and the longer the deflagration ashes takes to break out and close in on the opposite pole to collide. To test the GCD explosion model, we then performed a high-resolution (5123 computational zones) simulation for a model with an ignition spot offset near the upper limit of what is still justifiable, 200 km. This high-resolution simulation met our deliberately optimistic detonation criteria, and we initiated a detonation. The detonation burned through the white dwarf and led to its complete disruption. For this model, we determined detailed nucleosynthetic yields by post-processing 106 tracer particles with a 384 nuclide reaction network, and we present multi-band light curves and time-dependent optical spectra. We find that our synthetic observables show a prominent viewing-angle sensitivity in ultraviolet and blue wavelength bands, which contradicts observed SNe Ia. The strong dependence on the viewing angle is caused by the asymmetric distribution of the deflagration ashes in the outer ejecta layers. Finally, we compared our model to SN 1991T. The overall flux level of the model is slightly too low, and the model predicts pre-maximum light spectral features due to Ca, S, and Si that are too strong. Furthermore, the model chemical abundance stratification qualitatively disagrees with recent abundance tomography results in two key areas: our model lacks low-velocity stable Fe and instead has copious amounts of high-velocity 56Ni and stable Fe. We therefore do not find good agreement of the model with SN 1991T.

Rational design of a (S)-selective-Transaminase for asymmetric synthesis of (1S)-1-(1,1'-biphenyl 2-yl)ethanamine

Amine transaminases offer an environmentally sustainable synthesis route for the production ofpure chiral amines. However, their catalytic efficiency towards bulky ketone substrates isgreatly limited by steric hindrance and therefore presents a great challenge for industrialsynthetic applications. Hereby we report an example of rational transaminase enzyme design tohelp alleviate these challenges. Starting from the Vibrio fluvialis amine transaminase that has nodetectable catalytic activity towards the bulky aromatic ketone 2-acetylbiphenyl, we employed arational design strategy combining in silico and in vitro studies to engineer the transaminaseenzyme with a minimal number of mutations, achieving an high catalytic activity and highenantioselectivity. We found that by introducing two mutations W57G/R415A detectableenzyme activity was achieved. The rationally designed best variant,W57F/R88H/V153S/K163F/I259M/R415A/V422A, showed an improvement in reaction rateby > 1716-fold towards the bulky ketone under study, producing the corresponding enantiomericpure (S)-amine (ee value of > 99%).