2-Aminopyridines scaffolds are an important class of nitrogen heterocyclic compounds with a wide range of biological activities^1-2 (Figure 1). Multicomponent reactions (MCRs) are useful method for the construction of nitrogen heterocyclic compounds. In this context, syntheses of 2-aminopyridines derivatives via MCRs have attracted considerable attentions in recent years^3-4.

We present, in this work, a rapid and efficient synthesis of 2-aminopyridines derivatives, via catalyst-free four-component method. This protocol provides a simple and practical approach to functionalized 2-aminopyridnes from readily available substrates under solvent free conditions.

SeO₂ based samples are tested for the oxidation of α-pinene, in liquid phase employing ethanol as the solvent. Commercial SeO₂ was tested both, under reflux and under 6 atm O₂ pressure. At conversion levels of approximately 40%, the yield to myrtenal was much higher in the latter (34.4%) than in the former case (18.0%) due to the high oxidant species availability. Besides the high yield is attained at relatively short reaction time. Palladium promoted selenium dioxide supported catalyst (Pd/SeO₂/SiO₂) was prepared, characterized and submitted to the catalytic test. Selenium dioxide (14.4%) was strongly fixed to the silica support. Upon the palladium introduction (0.98%) the reducibility of SeO₂ is modified, which originates a selenium species activation towards the allylic oxidation. A 12% conversion level is attained over Pd/SeO₂/SiO₂ following 8 h of reaction time, employing ethanol as the solvent at 130°C. The main product is myrtenal, obtained with a selectivity of 62%. Over oxidation products are not detected. The palladium/selenium dioxide sample is easy to handle with and its recuperation following the reaction in liquid phase is possible.

Benzophenoxazine fluorophores, including derivatives of Nile Blue, one of the best known in this family of compounds, have been used as histological stains due to their optical properties in the NIR region and stability. Given their potential, the synthesis of two new Nile Blue derivatives with different substituents on the amines of the positions 5 and 9 was performed, with the introduction of a sulfonamide group in one of the compounds. Photophysical properties of the compounds were evaluated in acidified ethanol and aqueous solution at physiological pH. The fluorescent staining capacity was evaluated by staining Saccharomyces cerevisiae with the compounds, followed by fluorescence microscopy.

A small library of 1,2,3-triazoles was synthesized from diverse alkynes and azides using catalytic amounts of an alkynylcopper (I) complex which in turn was prepared from direct treatment of phenylacetylene with Fehling reagent in presence of glucose as reducing agent. The results suggest that CuAAC reaction requires only 0.5 mg/mmol copper (I) phenylacetylide without any further additives.

Coumarin and coumarin derivatives are bioactive compounds that have an important role in medicinal chemistry, for example in the development of anti-inflammatory, anticancer and antiviral drugs. These compounds arealso very powerful antioxidants that successfully scavenge free radicals and prevent or aleviate oxidative stress. The antioxidant potential of selected heterocyclic compounds containing coumarin core was investigated theoretically, the focus of this study was on hydrogen atom transfer mechanism (HAT) and sequential electron transfer followed by proton transfer mechanism (SET-PT). Using MOPAC2012 PM7, reaction enthalpies related to the cleavage of O–H, N–H and C–H bonds via selected mechanisms of free radical scavenging were studied and calculated. The effect of the position of the hydroxyl group, as well as other functional groups, on the antioxidant activity was examined. Based on obtained results, Schiff bases, thiosemicarbazides, oxadiazoles and 4-thiazolidinones containing one or more OH– groups exhibit higher radical scavenging properties.

Invasive pathologies have become an increasing threat to forestry and related industries. Pine wilt disease (PWD) destroys tree vascular tissues and resin canals inducing pine needle chlorosis and shoot wilting. It was introduced in Europe in 1999, probably through imported wood products from Asian countries. Despite the numerous control strategies, its causal agent, the pinewood nematode (PWN), Bursaphelenchus xylophilus, continues to spread at an alarming rate. Pest control based on trunk injection of nematicidal compounds remains the most effective and reliable containment strategy. Nevertheless, large spectrum nematicides can be dangerous to human health and the environment. Highly active essential oils (EOs) were reported to reach higher in vitro efficiencies than common use nematicides. EOs can be composed of a wide array of secondary metabolites, in various proportions, with distinct anti-PWN activities. The present work screened the existing bibliography on detailed chemical composition and activity of the EOs used against the PWN. The abundance of each EO component was correlated with the respective EO anti-PWN activity. Monoterpenoids dominated the structures with agonist or antagonist properties. Compounds showing transversal positive correlations were mainly alcohols and aldehydes while those showing negative correlations were hydrocarbons, ethers and ketones. Citronellol, a monoterpenic alcohol component of nine reported EOs, showed the best positive dose-response correlation, while the best negative correlation was identified for 1,8-cineole, a monoterpenic ether present in over 50 EOs. Using this transversal approach in EO nematicidal activity studies allows pinpointing highly active EO components and respective interactions with the PWN.

The constraints exerted on the molecular edifices by different environmental parameters are not the same, which is translated by different adaptive strategies. Thus, for the extracellular and periplasmic enzymes of marine organisms that are directly exposed to environments in which large variations in temperature and salinity can occur, it is not an easy task to separate the adaptation of the enzyme to one of the two environmental parameters without the involvement of the other. In such a scenario, a comparative study of a marine psychrophilic and an estuarine mesophilic endonuclease I was undertaken. The different salt optima of the enzymes were taken into consideration when the temperature-dependent enzymatic properties were characterized. But the results did not show an adaptive strategy at the molecular edifice. For that purpose, we employed multiple all-atom explicit solvent and ions molecular dynamics simulations, in conjunction with the different temperatures at the nanosecond time scale, to analyze the structural flexibility of the cold-adapted enzyme, the VsEndA, and its mesophile homologous, the VcEndA. The Root Mean Square Fluctuation (RMSF) profiles of the two enzymes are almost similar with the most flexible residues located at loop regions, for both enzymes. We underlined a different trend against temperature for the two enzymes. The cold-adapted enzyme was dominated by the lowest temperatures; T=300 and T=318K, compared to its warm adapted homologous for which the highest temperature studied, T=326K is the dominant one. The lifetimes of the hydrogen bonding network of most flexible residues of both enzymes correlate well with the RMSF of the considered enzymes.

Streptogramins are potent antibiotics against numerous highly resistant pathogens and therefore are used in last-resort human therapy. These antibiotics are formed of both A and B group compounds named Pristinamycins that differ in their basic primary structures.

Although Pristinamycin II_B is among the most interesting antibiotics in such a family, it presents numerous problems related to its chemical structure such as instability to most pHs, weak solubility in water, and resistance by bacteria.

As a response to the need of developing new antimicrobial agents, we have designed a new analog of Pristinamycin II_B, based most importantly on the introduction of fluorine atoms. We conjectured indeed that the introduced modifications may solve the above-mentioned problems exhibited by Pristinamycin II_B.

Our multistep synthetic approach relies on few key reactions, namely a Wittig reaction, a Grubbs reaction, and a dihydroxy, -difluoro API (Advanced Pharmaceutical Intermediate) synthesis.

Dicationic ionic liquids present a novel class of ionic liquids composed of a dication and two monoanions, the latter have shown an increasing interest in recent years and they used in numerous applications.

In comparison with conventional ionic liquids, the physicochemical properties of dicationic ionic liquids can be adjusted by modifying the languor and the type of chains connecting the cationic heads as well as the type of cation. This could give rise to symmetrical or asymmetrical dicationic ionic liquids.

In this work, we present a new synthesis of three imidazolium based dicationic ionic liquids, with two stages, the first is a quaternization reaction or the first dicationic ionic liquid was obtained with iodide ion.

The characterization of the dicationic ionic liquids was carried out by magnetic resonance spectroscopy allowing better identification of the products obtained.

In the development of new prostaglandin analogues, the most beneficial modifications for obtaining prostaglandin (PG) analogs with different biological activities have been done in the w-side chain. This chain is introduced, in the well known total stereo-controlled Corey convergent synthesis of PGs, by using a key β-ketophosphonate in an E-HEW-stereoselective olefination with an aldehyde linked to a key cyclopentane intermediate. The concept of PG w-side chain is design in the β-ketophosphonate intermediate. In vivo, the PGs are inactivated by enzyme oxidation of the 15-α-OH group to 15-keto group. By using 15-, 16- substituents or 16-aryloxy substituents, the inactivation was diminished. In this direction, we intend to diminish inactivation by introducing bulky bicyclo[3.3.0]octane or bicyclo[3.3.0]oct-6-ene substituents linked to the C-15 carbon atom. For this goal we synthesize the key β-ketophosphonate intermediates starting from bicyclo[3.3.0]oct(a)ene acids by a two or three step sequence. Two mono-acid β-ketophosphonates, one ester β-ketophosphonate and a bis-β-ketophosphonate compounds were obtained. The ester β-ketophosphonate was used to build the w-side chain of the concepted PG analog. The bis-β-ketophosphonate will create a pseudo PG compound with two PG fragments linked to a bicyclo[3.3.0]octane fragment. The compounds were characterized by elemental analysis, IR and high resolution ¹H- and ¹³C-NMR spectroscopy.