RESUMEN
The racemic title compound, C34H32OS2, comprises an atropisomeric binaphthyl di-thio-acetal substituted at the methyl-ene carbon atom with a chiral benzyl alcohol. The two naphthalene ring systems are additionally substituted at the 3,3'-position with isopropyl groups. The overall stereochemistry is defined as aS,R and aR,S. The hydroxyl group forms an intra-molecular O-Hâ¯S hydrogen bond to one of the sulfur atoms. The crystal structure contains weak C-Hâ¯π inter-actions that link the mol-ecules into extended arrays.
RESUMEN
The closely related title compounds, 1-(di-naphtho-[2,1-d:1',2'-f][1,3]dithiepin-4-yl)-2,2-di-methyl-propan-1-ol, C26H24OS2, 1 and 2-(di-naphtho-[2,1-d:1',2'-f][1,3]dithiepin-4-yl)-3,3-di-methyl-butan-2-ol, C27H26OS2, 2, both comprise an atrop-isomeric binaphthyl di-thio-acetal unit substituted at the methyl-ene carbon atom with a chiral neopentyl alcohol grouping. The overall stereochemistry of the racemate in each case is defined as aS,R and aR,S. In 1, the hydroxyl group generates inversion dimers via pairwise inter-molecular O-Hâ¯S hydrogen bonds whereas in 2, the O-Hâ¯S link is intra-molecular. Weak C-Hâ¯π inter-actions link the mol-ecules into extended arrays in both structures.
RESUMEN
Antimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol's primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the 'urgent threat' pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.
Asunto(s)
Antibacterianos/farmacología , Cannabidiol/análogos & derivados , Cannabidiol/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Animales , Antibacterianos/química , Cannabidiol/química , Cannabidiol/toxicidad , Clostridioides difficile/efectos de los fármacos , Farmacorresistencia Bacteriana/efectos de los fármacos , Femenino , Células HEK293 , Hemólisis/efectos de los fármacos , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones Endogámicos , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/efectos de los fármacos , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Relación Estructura-ActividadRESUMEN
Palladium-catalyzed reactions of aryl bromides and chlorides with two common stabilized carbanions-enolates of dialkyl malonates and alkyl cyanoesters-are reported. An exploration of the scope of these reactions was conducted, and the processes were shown to occur in a general fashion. Using P(t-Bu)(3) (1), the pentaphenylferrocenyl ligand (Ph(5)C(5))Fe(C(5)H(4))P(t-Bu)(2) (2), or the adamantyl ligand (1-Ad)P(t-Bu)(2) (3), reactions of electron-poor and electron-rich, sterically hindered and unhindered aryl bromides and chlorides were shown to react with diethyl malonate, di-tert-butyl malonate, diethyl fluoromalonate, ethyl cyanoacetate, and ethyl phenylcyanoacetate. Although alkyl malonates and ethyl alkylcyanoacetates did not react with aryl halides using these catalysts, the same products were formed conveniently in one pot from diethylmalonate by cross-coupling of an aryl halide in the presence of excess base and subsequent alkylation.