Search Results (7)

The emergence of RNA viruses driven by global population growth and international trade highlights the urgent need for effective antiviral agents that can inhibit viral replication. Nucleoside analogs, which mimic natural nucleotides, have shown promise in targeting RNA-dependent RNA polymerases (RdRps). Starting from protected 5-iodouridine, we report the synthesis of hitherto unknown C5-substituted-(1,3-diyne)-uridines nucleosides and their phosphoramidate prodrugs. The modifications at C5 include 4-(trifluoromethyl)benzene (a), 4-pentyl-benzene (b), 3,5-dimethoxy-benzene (c), 4-(trifluoromethoxy)benzene (d), 3-aniline (e), 4-pyridine (f), 3-thiophene (g), C₆H₁₃ (h), 2-pyrimidine (i), cyclopropyl (j), and phenyl (k) groups. These compounds were synthesized using Sonogashira palladium-catalyzed reactions and nickel–copper-catalyzed C-H activation between various alkynes, yielding between 25% and 67%. The antiviral activities of obtained compounds were measured through HTS against RNA viruses including influenza H1N1 and H3N2, human respiratory syncytial virus (RSV), SARS-CoV-2, Zika, hepatitis C virus (HCV), Hepatitis E virus (HEV), as well as against coronavirus (HCoV-229E). Unfortunately, none of them showed promising antiviral activity, with less than 85% inhibition observed in the cell viability screening of infected cells. Full article

Under certain conditions, ultrasonic treatment of certain foods and ingredients can contribute to the appearance of an extraneous odor, which is not usual for them, especially in fat-containing products. Since the food sector uses high-intensity ultrasound to control the crystallization of fats, the development of foreign smells and secondary fat oxidation products may impact the quality and safety of such items. In this work, we studied the volatile compounds’ profiles of oleogels structured with individual fractions of beeswax using ultrasonic treatment. For this work, six samples of oleogels were obtained. Sunflower oil was used as a fatty base, and three fractions of beeswax were used as gelators: hydrocarbon fraction (>99%), monoester fraction (>95%), and a mixture fraction of wax di- and triesters (10.1%), free fatty acids (40.1%), and free fatty alcohols (49.8%). The influence of ultrasonic treatment on the properties of oleogels was assessed using light microscopy in polarized light, texture analysis, gas chromatography with flame ionization, and mass spectrometric detection. Ultrasonic treatment affected the crystallization of oleogels and led to the formation of smaller crystals. At the same time, sonication led to both an increase and a decrease in the firmness of oleogels, depending on the composition of the gelator. As regards volatile compounds, a total of 121 fragrant substances were identified in all samples, including such groups as alkanes, alkenes, alkadienes, alkynes, alkadiynes, alcohols, ketones, aldehydes, terpenes, alkyl alkane, and alkyl benzene derivatives. Ultrasonic treatment caused formation of new volatile unsaturated compounds. Some of them are known to have an unpleasant odor and thus might be responsible for the extraneous odor formation in studied fatty systems. Those were mainly (E)-2-octene, 1-heptene, 1,3-butadiene, and 1,3-octadiene in all oleogel samples. Sonicated samples B and C additionally had but-1-en-3-yne, pentenyne, and 1,3-butadiyne, whose odor can also be characterized as extraneous and distasteful. Several volatile compounds, supposed to be products of lipid oxidation, were also identified. Here we assume a reasonable approach is needed when selecting sonication conditions to prevent undesirable taste and flavor in oleogels and oleogel-based food products. Full article

In today’s global plan to completely eradicate hepatitis C virus (HCV), the essential list of medications used for HCV treatment are direct-acting antivirals (DAAs), as interferon-sparing regimens have become the standard-of-care (SOC) treatment. HCV nonstructural protein 5A (NS5A) inhibitors are a very common component of these regimens. Food and Drug Administration (FDA)-approved NS5A inhibitors, although very potent, do not have the same potency against all eight genotypes of HCV. Therefore, this study aims to synthesize NS5A inhibitor analogues with high potency pan-genotypic activity and high metabolic stability. Starting from an NS5A inhibitor scaffold previously identified by our research group, we made several modifications. Two series of compounds were created to test the effect of changing the length and spatial conformation (para-para vs. meta-meta-positioned bis-imidazole-proline-carbamate), replacing amide groups in the linker with imidazole groups, as well as different end-cap compositions and sizes. The frontrunner inhibits genotype 1b (Con1) replicon, with an EC₅₀ value in the picomolar range, and showed high genotypic coverage with nanomolar range EC₅₀ values against four more genotypes. This together with its high metabolic stability (t½ > 120 min) makes it a potential preclinical candidate. Full article

Metal-catalyzed hydrofunctionalization reactions of alkynes, i.e., the addition of Y–H units (Y = heteroatom or carbon) across the carbon–carbon triple bond, have attracted enormous attention for decades since they allow the straightforward and atom-economic access to a wide variety of functionalized olefins and, in its intramolecular version, to relevant heterocyclic and carbocyclic compounds. Despite conjugated 1,3-diynes being considered key building blocks in synthetic organic chemistry, this particular class of alkynes has been much less employed in hydrofunctionalization reactions when compared to terminal or internal monoynes. The presence of two C≡C bonds in conjugated 1,3-diynes adds to the classical regio- and stereocontrol issues associated with the alkyne hydrofunctionalization processes’ other problems, such as the possibility to undergo 1,2-, 3,4-, or 1,4-monoadditions as well as double addition reactions, thus increasing the number of potential products that can be formed. In this review article, metal-catalyzed hydrofunctionalization reactions of these challenging substrates are comprehensively discussed. Full article

New catalytically or high pressure activated reactions and routes, including coupling, double bond migration in allylic systems, and various types of cycloaddition and dihydroamination have been used for the synthesis of novel bithiophene derivatives. Thanks to the abovementioned reactions and routes combined with non-catalytic ones, new acetylene, butadiyne, isoxazole, 1,2,3-triazole, pyrrole, benzene, and fluoranthene derivatives with one, two or six bithiophenyl moieties have been obtained. Basic sources of crucial substrates which include bithiophene motif for catalytic reactions were 2,2'-bithiophene, gaseous acetylene and 1,3-butadiyne. Full article

Cycloaddition reactions of alkynes are elegant, atom-efficient transformations for the synthesis of carbo- and heterocycles, mostly aromatic, involving the construction of challenging skeletons of complex molecules. Therefore significant efforts have recently been devoted to the development of novel methodologies, efficient strategies and different catalytic systems to broaden the scope of these reactions. We summarize in this review the recent advances in the cycloaddition reactions of 1,3-butadiynes to provide facile and reliable approaches to various functionalized carbo- and heterocycles. Full article

A conjugated-bisimidazolylporphyrin bridged by bis(ethynylfluorene) was synthesized and organized into linear polymer through self-coordination having mean molecular weights, M_w and M_n, of ~2.1 × 10⁵ Da and ~1.6 × 10⁵ Da, respectively. A large two-photon absorption cross section value of 3.4 × 10⁵ GM (per dimer unit) was observed. This value was comparable to that of the previously reported self-assembled linear polymer consisting of butadiyne-bridged imidazolylporphyrins. The two-photon absorption properties could be controlled by tuning the wavelength and absorption intensity of the one-photon absorption. Full article