Stereoselective hydrogenation of methylcyclohex-2-ene-1,4-diols used in the synthesis of ampelomins and deoxy-carbasugars

Stereoselective hydrogenation of methylcyclohex-2-ene-1,4-diols used as important intermediates for the preparation of ampelomins and deoxy-carbasugars was studied. These olefins were obtained in few steps from a chiral cis-diol resulting from microbial oxidation of toluene. Although the stereoselective hydrogenation of this type of substrates is difficult, high yields were obtained for heterogeneous hydrogenation using Adam’s catalyst, where steric hindrance controlled the stereochemical outcome of the process. On the other hand, for homogeneous hydrogenation of similar olefins using Crabtree’s catalyst, coordination with the allylic alcohols allowed for a controlled hydrogen addition from the more hindered face. In this manner two protocols for the hydrogenation of these types of substrates resulting in complementary stereoselectivities are described.     

Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads

We report not only the convergent total synthesis of falcitidin, a natural inhibitor of falcipain-2 from myxobacterium Chitinophaga, but also its diversification into a new antimalarial class of N-acyl tetrapeptides (Acyl-His-Ile-Val-Pro-NH₂). Despite the lack of whole-cell activity of falcitidin itself, our study led to the identification of a trifluoromethyl (CF₃) analogue displaying sub-micromolar IC₅₀ activity against Plasmodium falciparum 3D7 in a standard blood-cell assay, but only when N-tritylated on its histidine (imidazole) residue.     

Formal and total synthesis of (±)-cycloclavine

A ring fragmentation and intramolecular azomethine ylide 1,3-dipolar cycloaddition sequence of reactions was successfully used in the preparation of a known (±)-cycloclavine precursor in good overall yield. Results of efforts to incorporate the tetrasubstituted cyclopropane ring present in cycloclavine are also discussed.     

Synthetic studies directed toward the AB decalin common to HMP-Y1 and hibarimicinone

Efforts toward the synthesis of the decalin ring system common to the hibarimicin shunt metabolite HMP-Y1 and parent aglycone hibarimicinone are reported herein. An intramolecular Diels–Alder cyclization rapidly generated the decalin framework. Two approaches toward completion of the AB decalin were vetted. Incorporation of a phenylsulfonyl leaving group β- to both a ketone and a γ-lactone followed by base-induced elimination of sulfinate led to the undesired α,β-unsaturated lactone. Methanolysis of the γ-lactone followed by elimination produced the unexpected bridged cyclic ether by way of an intramolecular oxy-Michael addition of the endo oriented C13 alcohol.     

Total synthesis of (−)-Englerin A

A novel and efficient total synthesis of Englerin A is reported. The synthesis featured an intramolecular olefin metathesis ring closure reaction and a highly stereoselective oxygen bridge formation induced by an iodonium ion. This strategy can be used for the synthesis of natural products Englerin A and Englerin B and can provide flexibility in the preparation of various 9-substituted analogues of Englerin A for further structure–activity relationship studies.     

The synthesis of MCM-41 nanomaterial from Algerian Bentonite: The effect of the mineral phase contents of clay on the structure properties of MCM-41

This study focuses on the MCM-41 material (Mobil Composition of Matter). The MCM-41 nanomaterial presents higher physical properties such as pore sizes, surface areas and pore volumes. This material is usually synthesized by using laboratory reagents as silicate sources and aluminium source. These laboratory reagents are still expensive and toxic for large scale production. The main aim of this work is to resolve this problem and to replace these expensive laboratory reagents by more cost effective ones. The volclay and Algerian bentonite low-cost mass clay materials are used as silicate and acuminate sources separately by adopting an alkaline fusion process to extract both silicon and aluminium (1 kg of silicium and aluminium from volclay and Algerian bentonite cost around 0.03 and 0.01 € whereas the same amount of silicon from ludox and aluminium from sodium aluminates cost around 350 €). The synthesis of MCM-41 from bentonite was carried out by the hydrothermal method using the supernatants of bentonite (in the form of sodium silicate and sodium aluminate). On the basis of the data obtained from powder X-ray diffraction (XRD), transmission electron microscopy (TEM) and N₂ adsorption and desorption, the results revealed that the properties of MCM-41 synthesized from Algerian bentonite and volclay separately depend on both elemental composition and mineral phase contents of the used bentonite. Pure and highly ordered hexagonal mesoporous MCM-41 with uniform pore sizes and a high specific surface area have been successfully synthesized without any phases which exist in natural bentonite. The Algerian bentonite was chosen because of its low cost compared to volclay, another commercial clay source.     

Histone deacetylase (HDAC) inhibitor curcumin upregulates mitochondrial uncoupling protein1 (UCP1) and mitochondrial function in brown adipocytes,in-silico study and screening natural drug library

Mitochondrial dysfunction has been associated with diverse pathological conditions globally. Specifically, in adipose tissues, mitochondrial dysfunction is the primary cause of obesity and obesity-related illnesses. An existing drugs such as atorvastatin and other lipid-lowering drugs demonstrated adverse effects and initiated other diseases. Thus, we need to explore new methods to prevent and treat obesity. In this study, we used the cell screening method to identify several natural compounds that increase adipocyte UCP1 gene expression. The identified drug Curcumin was evaluated in cell models and the In-silico model. We found curcumin is an active compound of turmeric belonging to Zingiberaceae (ginger family), which activates the Nrf2 mechanism. Curcumin potentially endorses the expression of UCP1 in the brown adipocyte in vitro cellular model. Curcumin plays an important role that modulating mitochondrial function and improving mitochondrial DNA quantification, ATP production, and cell viability. We have established an efficient in vitro cell experiment system to study the metabolic regulation of UCP1. The in-silico model revealed curcumin-UCP1 interaction. Curcumin, via enhancing mitochondrial activity, could be a helpful therapeutic molecule against metabolic disorders or obesity-related diseases. Curcumin will be the subject of more research in both human and murine models, which will provide novel therapeutic pathways for the treatment of metabolic illnesses by modulating the control of mitochondrial function.     

In silico and in vivo study of adulticidal activity from Ayapana triplinervis essential oils nano-emulsion against Aedes aegypti

Nanoinsecticides of plant origin have advantages in the resistance of Aedes aegypti, vectors of infectious diseases. The objective of this study was to evaluate the insecticidal potential of Ayapana triplinervis essential oil nano-emulsions using in silico and in vivo assays in an Aedes aegypti model. Molecular docking showed that minority compounds present in the morphotype A essential oil have a more significant binding affinity to inhibit acetylcholinesterase and juvenile hormone receptors. Aedes aegypti adults were susceptible to A. triplinervis at 150 µg.mL-1 in a diagnostic time of 15 min for morphotype A essential oil nano-emulsion and 45 min for morphotype B essential oil nano-emulsion. The evaluation of toxicity in Swiss albino mice indicated that the nano-emulsions had low acute dermal toxicity and presented LD₅₀ greater than 2000 mg.Kg^?1. Thus, it is possible to conclude that nano-emulsions have the potential to be used in the chemical control of A. aegypti.     

Hydroxymethylated Phyllobilins: A Puzzling New Feature of the Dioxobilin Branch of Chlorophyll Breakdown

Colorless nonfluorescent chlorophyll (Chl) catabolites (NCCs) are formyloxobilin‐type phyllobilins, which are considered the typical products of Chl breakdown in senescent leaves. However, in degreened leaves of some plants, dioxobilin‐type Chl catabolites (DCCs) predominate, which lack the formyl group of the NCCs, and which arise from Chl catabolites by oxidative removal of the formyl group by a P450 enzyme. Here a structural investigation of the DCCs in the methylesterase16 mutant of Arabidopsis thaliana is reported. Eight new DCCs were identified and characterized structurally. Strikingly, three of these DCCs carry stereospecifically added hydroxymethyl groups, and represent bilin‐type linear tetrapyrroles with an unprecedented modification. Indeed, DCCs show a remarkable structural parallel, otherwise, to the bilins from heme breakdown.     

Damping analysis of nonwoven natural fibre-reinforced polypropylene composites used in automotive interior parts

The aim of this work is to evaluate the dynamic properties of nonwoven flax, hemp, kenaf and glass fibre-reinforced polypropylene (PP) composites. Also, the influence of some parameters, such as the type of reinforcement, the fibre/matrix weight ratio, the fibre orientation and the porosity content, on the damping behaviour of these nonwoven composites is investigated. To this end, a free flexural vibrations analysis was conducted to experimentally identify their natural frequencies and their associated loss factors. The obtained results show that the nonwoven composites reinforced by natural fibres present higher loss factors compared with those of the glass-PP composite. These interesting damping properties make these nonwoven composites very attractive for automotive applications where the dissipation of vibrations is highly requested.