Enantioselective Total Synthesis of (−)‐Blennolide A

Blennolide A can be synthesized through an enantioselective domino‐Wacker/carbonylation/methoxylation reaction of 7 a with 96 % ee and an enantioselective Wacker oxidation of 7 b with 89 % ee. Further transformations led to the α,β‐unsaturated ester (E)‐ 17 , which was subjected to a highly selective Michael addition, introducing a methyl group to give 18 a . After a threefold oxidation and an intramolecular acylation, the tetrahydroxanthenone 4 was obtained, which could be transformed into (?)‐blennolide A (ent‐ 1 ) in a few steps.     

Convenient and chromatography-free partial syntheses of maslinic acid and augustic acid

A convenient and chromatography-free 4-step synthesis of analytically pure maslinic acid (1, 41.2%) from oleanolic acid has been developed. Slight variations in the final steps gave an excellent yield of isomeric augustic acid (7, 71.9%).     

A surface oriented solid formulation based on a hybrid Galerkin-collocation method

The contribution is concerned with a numerical method to analyze the mechanical behavior of 3D solids. The method employs directly the geometry defined by the boundary representation modeling technique, which is frequently used in CAD to define solids. It combines the benefits of the isogeometric analysis methodology with the scaled boundary finite element method. In the present approach, only the boundary surfaces of the solid are discretized. No tensor-product structure of three-dimensional objects is exploited to parametrize the physical domain. The weak form is applied only on the boundary surfaces. The governing partial differential equations of elasticity are transformed to an ordinary differential equation (ODE) of Euler type. The isogeometric Galerkin approach is employed to approximate the displacement response at the boundary surfaces. It exploits the two-dimensional NURBS objects to parametrize the boundary surfaces. To solve the Euler type ODE, the NURBS based collocation approach is applied. The accuracy of the method is validated against the analytical solutions. The presented method is able to analyze solids, which are bounded by an arbitrary number of surfaces. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Light-Sensitive Phenacyl Crosslinked Dextran Hydrogels for Controlled Delivery**

Stimuli-responsive soft materials enable controlled release of loaded drug molecules and biomolecules. Controlled release of potent chemotherapeutic or immunotherapeutic agents is crucial to reduce unwanted side effects. In an effort to develop controlled release strategies that can be triggered by using Cerenkov luminescence, we have developed polymer hydrogels that can release bovine serum albumin and immunoglobulin G by using light (254 nm–375 nm) as a trigger. We describe the synthesis and photochemical characterization of two light sensitive phenacyl bis-azide crosslinkers that are used to prepare transparent self-supporting hydrogel patches. One crosslinker was designed to optimize the overlap with the Cerenkov luminescence emission window, bearing an π-extended phenacyl core, resulting in a high quantum yield (14 %) of photocleavage when irradiated with 375 nm light. We used the extended phenacyl crosslinker for the preparation of protein-loaded dextran hydrogel patches, which showed efficient and selective dosed release of bovine serum albumin or immunoglobulin G after irradiation with 375 nm light. Cerenkov-triggered release is as yet inconclusive due to unexpected side-reactivity. Based on the high quantum yield, efficient release and large overlap with the Cerenkov window, we envision application of these photosensitive soft materials in radiation targeted drug release.     

Between Two Chairs: Combination of Theory and Experiment for the Determination of the Conformational Dynamics of Xylosides

The conformational properties of monosaccharides constitute fundamental features of oligosaccharides. While the energy landscape of monosaccharides can be altered by a specific biochemical environment or by chemical modifications, the analysis of resulting dynamic conformational equilibria is not feasible by experimental means alone. In this work, a series of β-d -xylopyranosides is used to outline how a combination of experimental NMR parameters and computed molecular properties can be used to determine conformers and quantify the composition of conformational equilibria. We demonstrate that identifying the most stable conformers using energy calculations is challenging and computing of NMR shieldings is typically not sensitive enough. On the other hand, computed spin-spin coupling constants for the xyloside ring can be used to unambiguously assign experimental NMR data of dynamic conformational equilibria and quantify the ratio of different conformers in the mixture. As a proof of principle, this procedure allowed to analyze a hitherto unknown dynamic equilibrium of a diamino-xyloside as a precursor of a molecular switch.     

In Situ Grignard Metalation Method for the Synthesis of Hauser Bases

The in situ Grignard Metalation Method (iGMM) is a straightforward one-pot procedure to quickly produce multigram amounts of Hauser bases R₂N-MgBr which are valuable and vastly used metalation reagents and novel electrolytes for magnesium batteries. During addition of bromoethane to a suspension of Mg metal and secondary amine at room temperature in an ethereal solvent, a smooth reaction yields R₂N-MgBr under evolution of ethane within a few hours. A Schlenk equilibrium is operative, interconverting the Hauser bases into their solvated homoleptic congeners Mg(NR₂)₂ and MgBr₂ depending on the solvent. Scope and preconditions are studied, and side reactions limiting the yield have been investigated. DOSY NMR experiments and X-ray crystal structures of characteristic examples clarify aggregation in solution and the solid state.     

Photocatalytic Reduction of Nicotinamide Co-factor by Perylene Sensitized RhIII Complexes**

The ambitious goal of artificial photosynthesis is to develop active systems that mimic nature and use light to split water into hydrogen and oxygen. Intramolecular design concepts are particularly promising. Herein, we firstly present an intramolecular photocatalyst integrating a perylene-based light-harvesting moiety and a catalytic rhodium center ( Rh^IIIphenPer ). The excited-state dynamics were investigated by means of steady-state and time-resolved absorption and emission spectroscopy. The studies reveal that photoexcitation of Rh^IIIphenPer yields the formation of a charge-separated intermediate, namely Rh^IIphenPer ⋅ ⁺ , that results in a catalytically active species in the presence of protons.     

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column–ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power—a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury.     

Methane dissociation on Ni(111): the role of lattice reconstruction

The effects of lattice motion and reconstruction on the dissociation of methane on Ni(111) are explored, using both electronic structure theory and quantum dynamical calculations. We show that during the reaction, the Ni lattice reconstructs, effectively lowering the barrier to reaction, in contrast with earlier models of this process.