Investigation of macrocyclisation routes to 1,4,7-triazacyclononanes : efficient syntheses from 1,2-ditosylamides

Two routes to the synthesis of a cyclohexyl-fused 1,4,7-triazacyclononane involving macrocyclisations of tosamides have been investigated. In the first approach, using a classic Richman-Atkins-type cyclisation of a cyclohexyl-substituted 1,4,7-tritosamide with ethylene glycol ditosylate, afforded the cyclohexyl-fused 1,4,7-triazacyclononane in 5.86% overall yield in four steps. The second, more concise, approach involving the macrocyclisation of trans-cyclohexane-1,2-ditosamide with the tritosyl derivative of diethanolamine initially gave poor yields (< 25%). The well-documented problems with efficiencies in macrocyclisations using 1,2-ditosamides led to the use of a wider range of 1,2-ditosamides including ethane-1,2-ditosamide and propane-1,2-ditosamide. These extended studies led to the development of an efficient macrocyclisation protocol using lithium hydride. This new method afforded 1,4,7-tritosyl-1,4,7-triazacyclononanes in good yield (57-90%) from 1,2-ditosamides in a single step. These efficient methods were then applied to the preparation of a chiral cyclohexyl-fused 1,4,7-tritosyl-1,4,7-triazacyclononane (65-70%). This key chiral intermediate was then converted into a copper(II) complex following detosylation and N-methylation. The resulting chiral copper(II) complex catalysed the aziridination of styrene but it did so in a racemic fashion

Determination of the Primary Molecular Target of 1,2,4-Triazole-Ciprofloxacin Hybrids

We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.This research was supported by the Ministry of Science and Higher Education under Iuventus Plus grant No. IP2014 037473. Tomasz Plech is a recipient of the Fellowship for Young Researchers with Outstanding Scientific Achievements from the Medical University of Lublin (Lublin, Poland)

Analisis Kualitatif dan Kuantitatif Minyak Atsiri Dari Bunga Kamboja Putih (Plumeria acuminata W.T.Ait.) dan Bunga Kamboja Merah (Plumeria rubra L.)

Telah dilakukan penelitian untuk menganalisis secara kualitatif dan kuantitatif minyak atsiri bunga kamboja putih (Plumeria acuminata W.T.Ait.) dan bunga kamboja merah (Plumeria rubra L.). Hasil uji kualitatif minyak atsiri bunga kambojaputih meliputi bentuk cair, bau khas aromatik bunga kamboja, warna kuning muda, rasa manis agak pedas, bobot jenis 0,6956 ± 0,0217, indeks bias (nD250) = 1,4788 ± 10-04 dan kadar minyak atsiri0 0,12 ± 0,02%(v/b). Minyak atsiri bunga kamboja merah memiliki bentuk cair, bau khas aromatik bunga kamboja, warna jingga kecoklatan,rasa manis agak pedas, bobot jenis 0,3844 ± 0,005, indeks bias (nD250) = 1,4197 ± 10-04 dan kadar minyak atsiri 0,09 ± 0,03%(v/b). Noda KLT masing-masing menunjukan jumlah yang sama yaitu terdapat 8 noda. Analisis KG-SM menunjukkan bahwa minyak atsiri atsiri bunga kamboja putih memiliki 19 senyawa dengan area lebih dari 1% tapi yang teranalisis didominasi oleh 5 komponen senyawa antara lain Pentakosan (5,69%), Heksakosan (4,88%), Benzil alkohol (4,35%), Tetrakosan (4,18%), dan Heptakosan (3,01%). Minyak atsiri atsiri bunga kamboja merah memiliki 17 senyawa dengan area lebih dari 1 %, 5 komponen senyawa yang mendominasi antara lain Feniletilalkohol (12,43%), Benzenasetonitril (6,30%), Pentakosan (3,48%), Tetrakosan (3,14%), dan Trikosan (2,27%). Kandungan yang sama pada kedua jenis minyak atsiri adalah Pentakosan dan Tetrakosan dalam jumlah berbeda

Glycerol as a cheap, safe and sustainable solvent for the catalytic and regioselective β,β-diarylation of acrylates over palladium nanoparticles

Herein we show that glycerol can be considered as a promising cheap and green solvent for the regioselective β,β-diarylation of alkenes. Whereas this reaction is generally catalyzed under an inert atmosphere by expensive phosphine or carbene-palladium complexes, we show here that the diarylation of alkenes can be conveniently achieved in glycerol in the presence of air-stable palladium nanoparticles. These palladium nanoparticles were stabilized over a sugar-based surfactant derived from biomass. By an adjustment of the reaction temperature, we were able to control the mono- and diarylation step of alkenes, thus offering a convenient route to unsymmetrical diarylated alkenes. At the end of the reaction, the diarylated alkenes were cleanly and selectively extracted from the glycerol-palladium catalytic phase using supercritical carbon dioxide, thus affording a convenient purification work-up. Within the framework of green chemistry, this work combines (i) catalysis in a cheap, safe and sustainable medium, (ii) easily made and air-stable palladium nanoparticles as the catalyst, and (iii) a clean and selective extraction of the reaction products with supercritical carbon dioxide

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

Conjugating binary systems for spacecraft thermal control

The materials search was directed to liquid pairs which can form hydrogen bonds of just the right strength, i.e., strong enough to give a high heat of mixing, but weak enough to enable phase change to occur. The cursory studies performed in the area of additive effects indicate that Conjugating Binary (CB) performance can probably be fine-tuned by this means. The Fluid Loop Test Systems (FLTS) tests of candidate CBs indicate that the systems Triethylamine (TEA)/water and propionaldehyde/water show close to the ideal, reversible behavior, at least initially. The Quick Screening Tests QSTs and FLTS tests, however, both suffer from rather severe static due either to inadequate stirring or temperature control. Thus it is not possible to adequately evaluate less than ideal CB performers. Less than ideal performers, it should be noted, may have features that make them better practical CBs than ideal performers. Improvement of the evaluation instrumentation is thus indicated

New cobalt(I) complexes derived from dicarbonyltricyanocobaltate(I)

The preparation and characterization of several series of mixed ligand cobalt(I) complexes of the types [Co(CN)_2(CO)_2(PR_3)]–, [Co(CN)_2(CO)(PR_3)_2]–, and [Co(CN)(CO)_2(PR_3)_2], prepared by the reactions of tertiary phosphines (PR_3) with [Co(CN)_3(CO)_2]^(2–), are described and some novel aspects of their chemistry are discussed