Enantiospecific Synthesis and Cytotoxicity Evaluation of Oximidine II Analogues

Analogues of the anticancer natural product oximidine II were prepared and evaluated for cytotoxicity. One analogue of oximidine II that carries a C15 allylic amide side chain as well as two analogues with C15 vinyl sulfone side chains were found to lack cytotoxicity against the cancer cell line SK‐Mel‐5, thereby confirming the necessity of the C15 enamide side chain of oximidine II for cytotoxicity. Four analogues, designed by comparative molecular similarity index analysis (CoMSIA), that feature a less complex macrolactone scaffold were prepared and tested. The two analogues carrying a C15 vinyl sulfone group and the two analogues with a C15 oximidine II enamide side chain showed weak cytotoxicity against the SK‐Mel‐5 cell line and other cell lines, indicating that the designed simplified macrocycles cannot replace the oximidine II macrocycle.     

Short fiber-reinforced oxide fiber composites

This paper presents a novel fiber spraying process for the manufacturing of short fiber bundle-reinforced Nextel™ 610/Al₂O₃-ZrO₂ oxide fiber composites (SF-OFC) and its characterization. First, the influence of varying fiber lengths (7, 14, and 28 mm, continuous fibers) and fiber orientations (unidirectional 0°, quasi-isotropic, ±45°) was investigated using hand-laid SF-OFC. Due to the weak matrix, the hand-laid material exhibited a strongly fiber-dominated material behavior, that is, variations in fiber length and orientation had a strong influence on the material properties. Second, the automated sprayed SF-OFC, however, exhibited a random orientation of the fiber bundles, which resulted in in-plane isotropic material properties. Average bending strengths of up to 177 MPa, strains of .39%, and a quasi-ductile fracture behavior were achieved. The strain was, therefore, in the range of fabric-reinforced OFC. While the bending strength of the SF-OFC was somewhat lower than that of fabric-reinforced OFC with the fiber orientation parallel to the loading direction, it was more than two times higher than the strength in 45° direction relative to the fabric reinforcement. Combined with good drapability and lower material costs compared to fabric-reinforced OFC, SF-OFC is, therefore, a promising material for industrial applications.     

Modeling and in-depth analysis of the start-up of dividing-wall columns

Saving potentials of up to 30% in capital and operating costs are the driving forces behind the increase in the application of dividing-wall columns in industry. However, a lack of knowledge still exists when dealing with the start-up of dividing-wall columns, which is inherently a strongly nonlinear process. Here, for the first time the start-up of dividing-wall columns is explored, where the starting point is an empty column at ambient conditions. A model is presented which is capable of predicting the dynamic discrete-continuous changes which are characteristic of dividing-wall columns. The proposed process model takes into account the heat transfer across the dividing wall as well as the vapor distribution below the dividing wall. The degree of accuracy of the model is clearly determined by comparing different simplifications, e.g. a constant vapor distribution ratio equal to the steady-state value. The detailed studies were carried out with strict product specifications so that the influence of process parameters could be quantified. The rigorous process model and the obtained simulation results presented in this study provide a promising basis for developing and applying optimal start-up policies for dividing-wall columns.     

Rapid detection of vegetable oils in milk fat by on‐line LC‐GC analysis of β‐sitosterol as marker

On‐line liquid chromatography‐gas chromatography (LC‐GC) has been applied to the detection of vegetable oils in milk fat using β‐sitosterol as marker. The method involves transesterification of the fat, pre‐separation of the sterol fraction from other lipid constituents and on‐line transfer to the capillary GC system. The on‐line approach avoids time‐consuming sample preparation steps prior to GC analysis. The suitability of this analytical approach was tested with model mixtures of milk fat with cotton and rapeseed oil. The method allows the detection of adulterations at low levels. Simultaneous quantification of cholesterol in milk fat is also possible. Considering the rapid sample preparation, the described method can be applied for screening of large sample numbers.     

Comparison of the wound-activated transformation of caulerpenyne by invasive and noninvasive Caulerpa species of the Mediterranean

The invasive green alga, Caulerpa taxifolia, that has spread rapidly after its introduction into the Mediterranean and the North American Pacific, reacts to wounding by transforming its major metabolite caulerpenyne (1). This wound-activated reaction involves the transformation of the bis-enol acetate moiety of 1, releasing reactive 1,4-dialdehydes. The ability to perform this transformation is found also in both the noninvasive Mediterranean C. prolifera and the invasive C. racemosa. Trapping experiments, as well as transformation of the model substrate geranyl acetate, suggest that all three investigated Caulerpa spp. rely on esterases that act upon wounding of the algae by subsequently removing the three acetate residues of caulerpenyne. The resulting reactive 1,4-dialdehyde oxytoxin 2 (9) can be identified by liquid chromatography–mass spectrometry and is unstable in the wounded tissue. Caulerpenyne transformation occurs rapidly, and severe tissue damage caused degradation of more than 50% of the stored caulerpenyne within 1 min in all three algae. Prevention of the enzymatic reaction before extraction, by shock freezing the tissue with liquid nitrogen, was used for the determination of the caulerpenyne content in intact algae. It gives about twofold higher values compared to an established methanol extraction protocol. The speed and mechanism of the wound-activated transformation, as well as the caulerpenyne content in intact tissue of invasive and noninvasive Caulerpa spp., are comparable. Thus, this enzymatic , transformation, despite being fast and efficient, is likely not the key for the success of the investigated invasive species.     

Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

Mammalian-Like Inflammatory and Pro-Resolving Oxylipins in Marine Algae

Oxylipins constitute a family of oxidized fatty acids, that are well known as tissue hormones in mammals. They contribute to inflammation and its resolution. The major classes of these lipid mediators are inflammatory prostaglandins (PGs) and leukotrienes (LTs) as well as pro-resolving resolvins (Rvs). Understanding their biosynthetic pathways and modes of action is important for anti-inflammatory interventions. Besides mammals, marine algae also biosynthesize mammalian-like oxylipins and thus offer new opportunities for oxylipin research. They provide prolific sources for these compounds and offer unique opportunities to study alternative biosynthetic pathways to the well-known lipid mediators. Herein, we discuss recent findings on the biosynthesis of oxylipins in mammals and algae including an alternative pathway to prostaglandin E₂, a novel pathway to a precursor of leukotriene B₄, and the production of resolvins in algae. We evaluate the pharmacological potential of the algal metabolites with implications in health and disease.     

N-Substituted Nipecotic Acids as (S)-SNAP-5114 Analogues with Modified Lipophilic Domains

Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC₅₀ value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity.