RESUMEN
The electrophilic activation of various substrates via double or even triple protonation in superacidic media enables reactions with extremely weak nucleophiles. Despite the significant progress in this area, the utility of organophosphorus compounds as superelectrophiles still remains limited. Additionally, the most common superacids require a special care due to their high toxicity, exceptional corrosiveness and moisture sensitivity. Herein, we report the first successful application of the "Brønsted acid assisted Brønsted acid" concept for the superelectrophilic activation of 2-hydroxybenzo[e][1,2]oxaphosphinine 2-oxides (phosphacoumarins). The pivotal role is attributed to the tendency of the phosphoryl moiety to form hydrogen-bonded complexes, which enables the formation of dicationic species and increases the electrophilicity of the phosphacoumarin. This unmasks the reactivity of phosphacoumarins towards non-activated aromatics, while requiring only relatively non-benign trifluoroacetic acid as the reaction medium.
Asunto(s)
Compuestos Organofosforados , Catálisis , Compuestos Organofosforados/química , Enlace de Hidrógeno , Ácidos/química , Estructura MolecularRESUMEN
In contrast to hypervalent iodine compounds, the chemistry of their sulfur analogues has been considerably less explored. Herein, we report the direct C-H bond thiolation of electron-rich heterocycles, arenes, and 1,3-dicarbonyls by dichlorosulfuranes under mild conditions. Mechanistic studies and density functional theory calculations suggest the radical chain mechanism of the disclosed transformation. The key to success is attributed to a strikingly low S-Cl bond dissociation energy, which enables the generation of radical species upon exposure to daylight.
RESUMEN
Herein, we report a highly regioselective one-pot synthesis of pyrazolo[3,4-b]pyridines via the reaction of 3-arylidene-1-pyrrolines with aminopyrazoles. The reaction proceeds through the sequential nucleophilic addition/electrophilic substitution/C-N bond cleavage and provides easy access to pyrazolo[3,4-b]pyridine derivatives featuring a primary amino group. Moreover, the reaction can be terminated at the electrophilic substitution stage, thus providing convenient entry to the hardly accessible pyrazolopyrrolopyridine scaffold.
RESUMEN
Herein, we report the design and synthesis of novel 7-aza-coumarine-3-carboxamides via scaffold-hopping strategy and evaluation of their in vitro anticancer activity. Additionally, the improved non-catalytic synthesis of 7-azacoumarin-3-carboxylic acid is reported, which features water as the reaction medium and provides a convenient alternative to the known methods. The anticancer activity of the most potent 7-aza-coumarine-3-carboxamides against the HuTu 80 cell line is equal to that of reference Doxorubicin, while the selectivity towards the normal cell line is 9-14 fold higher.
Asunto(s)
Antineoplásicos , Antineoplásicos/farmacología , Relación Estructura-Actividad , Doxorrubicina , Cumarinas/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
Herein we present the regio- and diastereoselective synthesis of novel pyrrolidine-fused spiro-dihydrophosphacoumarins via intermolecular [3 + 2] cycloaddition reaction. The presented approach is complementary to existing ones and provides an easy entry to the otherwise inaccessible derivatives. Additionally, the unprecedented pathway of the reaction of 4-hydroxycoumarin with azomethine ylides is described. The anti-cancer activity of the obtained compounds was tested in vitro, the most potent compound being 2.6-fold more active against the HuTu 80 cell line than the reference 5-fluorouracil, with a selectivity index > 32.
Asunto(s)
Compuestos de Espiro , Compuestos de Espiro/farmacología , Estereoisomerismo , Reacción de CicloadiciónRESUMEN
The cooperative L-proline/Brønsted acid/base promoted reaction of 2-ethoxypyrrolidines or N-substituted 4,4-diethoxybutan-1-amines with methyl(alkyl/aryl)ketones for the synthesis of 2-(acylmethylene)pyrrolidine derivatives is reported. The key features of the developed protocol are gram-scale synthesis of the target compounds, easily available starting materials, operational simplicity and usage of non-expensive reagents.
Asunto(s)
Acetales , Alcaloides , Cetonas , Estructura Molecular , Pirrolidinas , EstereoisomerismoRESUMEN
The series of novel taurine-derived diarylmethanes and dibenzoxanthenes was synthesized starting from simple commercially available precursors via modular three-stage approach. All the newly synthesized compounds were screened for inâ vitro antibacterial and antifungal activity, as well as cytotoxicity towards normal and cancer cell lines. Some of the synthesized compounds exhibited 2-4-fold higher activity against S.â aureus, E.â faecalis and B.â cereus compared with Chloramphenicol. In contrast to Chloramphenicol, the tested compounds also showed bactericidal, rather than bacteriostatic effect, which makes them promising candidates for further studies.
Asunto(s)
Antiinfecciosos , Antineoplásicos , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Antifúngicos/farmacología , Antineoplásicos/farmacología , Cloranfenicol , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Staphylococcus aureus , Relación Estructura-Actividad , Taurina , XantenosRESUMEN
A series of novel 4-(het)arylimidazoldin-2-ones were obtained by the acid-catalyzed reaction of (2,2-diethoxyethyl)ureas with aromatic and heterocyclic C-nucleophiles. The proposed approach to substituted imidazolidinones benefits from excellent regioselectivity, readily available starting materials and a simple procedure. The regioselectivity of the reaction was rationalized by quantum chemistry calculations and control experiments. The anti-cancer activity of the obtained compounds was tested in vitro.
Asunto(s)
Antineoplásicos , Imidazolidinas/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Ciclización , Células HeLa , Humanos , Imidazolidinas/síntesis química , Imidazolidinas/farmacologíaRESUMEN
The approach to the novel 1-[(2-aminoethyl)sulfonyl]-2-arylpyrrolidines via unique intramolecular cyclization/aza-Michael reactions of N-(4,4-diethoxybutyl)ethenesulfonamide have been developed, which benefits from high yields of target compounds, mild reaction conditions, usage of inexpensive and low-toxic reagents, and allows for wide variability in both amine and aryl moieties. Biotesting with whole-cell luminescent bacterial biosensors responding to DNA damage showed that all tested compounds are not genotoxic. Tested compounds differently affect the formation of biofilms by Vibrio aquamarinus DSM 26054. Some of the tested compounds were found to suppress the bacterial biofilms growth and thus are promising candidates for further studies.