Phenazines Modulate Gastrointestinal Metabolism and Microbiota

Background: Natural and synthetic phenazines are ubiquitously occurred in environment and have been used for various therapeutic purposes in human, animals and agriculture, and the widespread use makes residue problem in environment and foods increasingly serious. However, the metabolic and comprehensive impacts of phenazines on the digestive tract are poorly understood, particularly the microbial pyocyanin (PYO), the most representative phenazines produced by Pseudomonas . Here, we utilized PYO as the representative of phenazines to study the effects on digestive tract. Results: Metabolic kinetic analysis showed that PYO exhibited low oral bioavailability in both rats and swine model, revealing a restriction of PYO in gut and might cause impacts on digestive tract. PYO was subsequently found to induce intestinal barrier destruction including inflammation and reactive oxygen species (ROS) accumulation in duodenum. Microbiome analysis showed that PYO caused gut microbiota dysbiosis by decreasing the symbiotic bacteria and increasing the opportunistic pathogenic bacteria. Additionally, the integral and dysfunctional assessment of liver demonstrated that PYO induced liver inflammation and metabolic disorder. Metabolism analysis further confirmed that PYO could be metabolized by both gut microbiota and liver, and all metabolites retained the nitrogen-containing tricyclic structural skeleton of phenazines, which was the core bioactivity of phenazine compounds, indicating all the outcomes were due to the intrinsic characteristic of phenazine structure. Conclusions: PYO were low oral bioavailable and all the metabolites retained the nitrogen-containing tricyclic structural skeleton, final resulting in the damages to digestive tract including intestinal barrier destruction, gut microbiota dysbiosis, liver damages and metabolic disorder. These findings elucidated the effect of phenazines on digestive tract in vivo and shed light on the rational design of phenazines for the development and application of such compounds in future.

Combinatorial Synthesis of Novel 1-Sulfonyloxy/acyloxyeugenol Derivatives as Fungicidal Agents

Background: Developing the high-efficiency and low-risk small-molecule green-fungicide is the key to effective control of the plant pathogenic oomycetes. Essential oils play a very important role in novel fungicide discovery for their unique sources and potential target sites. Eugenol, a kind of plant essential oil, was mainly isolated from the unopened and dried flower buds of Syzygium aromaticum of the Myrtaceae family. Due to its unique structural skeleton, eugenol and its derivatives have exhibited a wide range of biological activities. However, study on the synthesis of novel 1-sulfonyloxy/acyloxyeugenol derivatives as fungicidal agents against Phytophthora capsici has not yet been reported. Methods: Twenty-six novel 1-sulfonyloxy/acyloxyeugenol derivatives (3a-p and 5a-j) were prepared and their structures were well characterized by 1H NMR, HRMS, and m.p.. Their fungicidal activity was evaluated against P. capsici by using the mycelial growth rate method. Results: To find novel natural-product-based fungicidal agents to control the plant pathogenic oomycetes, we herein designed and synthesized two series of novel 1-sulfonyloxy/acyloxyeugenol derivatives (3a-p and 5a-j) as fungicidal agents against P. capsici Leonian, in vitro. Results of fungicidal activity revealed that, among all compounds, especially compounds 3a, 3f, and 3n displayed the most potent anti-oomycete activity against P. capsici with EC50 values of 79.05, 75.05, and 70.80, respectively. Conclusion: The results revealed that the anti-oomycete activity of eugenol with the sulfonyloxy group was higher than that with the acyloxy group. It is suggested that the fungicidal activity of eugenol can be improved by introducing the sulfonyloxy group. This will pave the way for further design, structural modification, and to develop eugenol derivatives as fungicidal agents.

BERLIN NEUE NATIONALGALERIE. A CONTEMPORARY VIEW OF THE MODERN TEMPLE

Mies van der Rohe´s approach to architecture through a poetic structural skeleton, abstractly refined to become a universal prototype of the essence of form and spiritualization of space, can be best seen at the Neue Nationalgalerie in Berlin. This unique modern temple recently under refurbishment by the subtle pencil of David Chipperfield [1] will soon have to be prepared to receive the extra additional space designed by the winner competition office leaded by Herzog & De Meuron [2]. Despite the rebirth of the building´s prestige there is still a gap of knowledge on the construction philosophy pursued by Mies van der Rohe, who conceived the Galeria Project as a phenomenological duality of lightness and heaviness in within a constant game of oppositions, exquisitely intended to intensify human emotions. Far beyond a mere construction, the magnificent museum became a place where the Silesia stone terrace seemed to detain the historical time meanwhile the biotite grey steel structure was encapsulating a flexible space embracing the dynamic elapse of life. The investigation undertaken by this author on the building´s original working drawings at the MvdR Archive in New York revealed unknown details which are helping nowadays to achieve a deeper understanding on the design and construction process of the iconic miesian museum. The underground ventilation channels running beneath the monolithic concrete plinth refreshing the interior volume with perfumed air from the garden´s lindens, altogether with the heroic columns and the freestanding glass membranes of the façades, resume today´s dilemma of the global high-tech city within the natural realm.

Contemporary advancements of semi-synthesis of bioactive terpenoids and steroids

Many natural products have intriguing biological properties that arise from their fascinating chemical structures. However, the intrinsic complexity of the structural skeleton and the reactive functional groups on natural products...

Stereoselective and Stereospecific Triflate Mediated Intramolecular Schmidt Reaction: Easy Access to Alkaloid Skeletons

The stereoselectivity and stereospecificity of the triflate mediated intramolecular Schmidt reaction of substituted 3-(1-azidocyclohexyl)propanol derivatives leading to octahydro-1<i>H</i>-pyrrolo[1,2-a]azepine, the structural skeleton of several important families of alkaloids such as the <i>Stemona</i> alkaloids, has been examined. The reaction involves an initial intramolecular S_N2 reaction between the azide moiety and the triflate affording an intermediate spirocyclic aminodiazonoium salt that undergoes the expected 1,2-shift/N₂-elimination followed by hydride mediated iminium salt reduction. Remarkably, chiral alcohols are converted to the azabicylic derivative with no or limited racemization. The initial asymmetric alcohol center controls the diastereoselectivity of the whole process leading to the formation of one out of the four possible diastereoisomers of disubstituted octahydro-1<i>H</i>-pyrrolo[1,2-a]azepine. The origin of the stereoselectivity is rationalized based on theoretical calculations. The concise synthesis of (–)-(<i>cis</i>)-3-propylindolizidine and (–)-(<i>cis</i>)-3-butyllehmizidine, two alkaloids found in the venom of workers of the ant <i>Myrmicaria melanogaster</i>, is reported.<br>

Stereochemical Control of the Triflate Mediated Intramolecular Schmidt Reaction

The stereoselectivity of the triflate mediated intramolecular Schmidt reaction of substituted 3-(1-azidocyclohexyl)propanol derivatives leading to octahydro-1<i>H</i>-pyrrolo[1,2-a]azepine, the structural skeleton of several important families of alkaloids such as the <i>Stemona</i> alkaloids, has been examined. The reaction involves an initial intramolecular S_N2 reaction between the azide moiety and the triflate affording an intermediate spirocyclic aminodiazonoium salt that undergoes the expected 1,2-shift/N₂-elimination followed by hydride mediated iminium salt reduction. Remarkably, chiral alcohols are converted to the azabicylic derivative with no or limited racemization. The initial asymmetric alcohol center controls the diastereoselectivity of the whole process leading to the formation of one out of the four possible diastereoisomers of disubstituted octahydro-1<i>H</i>-pyrrolo[1,2-a]azepine. The origin of the stereoselectivity of is rationalized based on theoretical calculations.

Stereochemical Control of the Triflate Mediated Intramolecular Schmidt Reaction

The stereoselectivity of the triflate mediated intramolecular Schmidt reaction of substituted 3-(1-azidocyclohexyl)propanol derivatives leading to octahydro-1<i>H</i>-pyrrolo[1,2-a]azepine, the structural skeleton of several important families of alkaloids such as the <i>Stemona</i> alkaloids, has been examined. The reaction involves an initial intramolecular S_N2 reaction between the azide moiety and the triflate affording an intermediate spirocyclic aminodiazonoium salt that undergoes the expected 1,2-shift/N₂-elimination followed by hydride mediated iminium salt reduction. Remarkably, chiral alcohols are converted to the azabicylic derivative with no or limited racemization. The initial asymmetric alcohol center controls the diastereoselectivity of the whole process leading to the formation of one out of the four possible diastereoisomers of disubstituted octahydro-1<i>H</i>-pyrrolo[1,2-a]azepine. The origin of the stereoselectivity of is rationalized based on theoretical calculations.

Antioxidant and Antidiabetic Activities of Flavonoid Derivative Compounds Isolated from Sclerocarya birrea Leaves

Sclerocarya birrea is one of many medicinal plants used in African traditional medicine for treatment of diabetes. Bioassay-guided fractionation of the ethanolic crude extract of the leaves of the plant species led to the isolation of a pure compound (CMP-1). The pure compound showed antioxidant and antidiabetic activities with average IC50 values of 1.04 mg/mL and 46 μg/mL, respectively that were well comparable to the crude extract and known standards compounds, ascorbic acid and quercetin. The spectroscopic profiling of the purified compound revealed a flavonoid derivative structural skeleton. The findings of the study suggested that the flavonoid derivative compounds play a major role towards the medicinal value of Sclerocarya birrea.

A Three-Dimensional Strain Rosette Sensor Based on Graphene Composite with Piezoresistive Effect

Obtaining the internal stress and strain state of concrete to evaluate the safety and reliability of structures is the important purpose of concrete structural health monitoring. In this paper, a three-dimensional (3D) strain rosette sensor was designed and fabricated using graphene-based piezoresistive composite to measure the strains in concrete structures. The piezoresistive composite was prepared using reduced graphene oxide (RGO) as conductive filler, cellulose nanofiber (CNF) as dispersant and structural skeleton, and waterborne epoxy (WEP) as polymer matrix. The mechanical, electrical, and electromechanical properties of RGO-CNF/WEP composite were tested. The results show that the tensile strength, elastic modulus, and conductivity of the composite are greatly improved by the addition of RGO and CNF. The relative resistance change of composite films demonstrates high sensitivity to mechanical strain with gauge factors of 16-52. Within 4% strain, the piezoresistive properties of composites are stable with good linearity and repeatability. The sensing performance of the 3D strain rosette was tested. The measured strains are close to the actual strains of measure point in concrete, and the error is small. The RGO-CNF/WEP composite has excellent mechanical and piezoresistive properties, which enable the 3D strain rosette to be used as embedded sensor to measure the internal strain of concrete structures accurately.