RESUMEN
A Rh(II)/boron reagent co-catalyzed unprecedent transformation was established for the rapid construction of multi-substituted conjugated dienones under mild conditions by trapping allene carbocations with oxonium ylides from simple starting points in yields up to 85%. Two CîC double bonds, one C-C and one C-O single bond were built in this one-pot reaction. The diversity-oriented strategy was also established to synthesize alkyne ether and dihydrofuran derivatives by a substrate-depended fashion.
RESUMEN
Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study affords the final water-soluble lead compound (R)-8i as a potential inhibitor for the proliferation of OS cells by the modulation of solubility of the compounds with remarkable cellular potency (IC50 = 21.9 nM for MNNG/HOS cells) and in vivo efficacy (52.9% inhibition OS growth in mice), as well as pharmacokinetic properties. (R)-8i also significantly suppresses OS cell migration in vitro and showed to be well-tolerated. Our preliminary investigation shows that the effects of (R)-8i are not dependent on p53 and myoferlin (MYOF). These results suggest that (R)-8i might be a potential drug candidate for OS treatment.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Piridinas/farmacología , Tiazolidinas/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Ratones Desnudos , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Osteosarcoma/patología , Piridinas/síntesis química , Piridinas/química , Relación Estructura-Actividad , Tiazolidinas/síntesis química , Tiazolidinas/químicaRESUMEN
A green and highly efficient one-pot method for α-diaryl-ß-alkynol derivatives in water at room temperature was developed using the cocatalysis of a Lewis acid and meso-tetraphenylporphyrin iron(III) chloride (FeTPPCl). The unprecedented transformation was promoted by a modulation of the charge properties of propargylic carbocation chemistry and the use of an in situ-generated oxonium ylide as a matching nucleophile. The reaction was performed in water at room temperature with a highly step-economic manipulation in good to excellent yields and with a broad substrate scope. Water also acts as the third reactant for the one-pot transformation. Notably, the FeTPPCl catalyst can be directly reused four times with a slight discount in yields.
RESUMEN
A Pd-catalyzed multicomponent reaction was developed by trapping oxomium ylide with nitrosobenzene via Pd-promoted umpolung chemistry. The Pd catalyst plays two important roles: diazo compound decomposed catalyst and Lewis acid for the activation of nitrosobenzene. This strategy provides some insight into a new way for discovery of multicomponent methodology to construct complex molecules. The developed method also provides rapid access to a series of O-(2-oxy) hydroxylamine derivatives, which exhibit good anticancer activity in osteosarcoma cells.
Asunto(s)
Oxígeno , Paladio , Catálisis , Ácidos de LewisRESUMEN
The C(sp2)-H function of indole ketone with diazo compound via a rhodium(II)-catalyzed intramolecular electrophilic trapping reaction under mild conditions in air was demonstrated. The established methodology provided a highly efficient approach for direct synthesis of mutisubstituted tetrahydrocarbazoles with continuous quaternary carbons. The resulting products facilitate further modification to conveniently construct tetrahydrocarbazoles with additional fused heterocyclic rings. By phenotypic screening, several products exhibit good anticancer bioctivities in osteosarcoma cell lines.
RESUMEN
The classic transformations of N-sulfonyl-1,2,3-triazoles were processed via nitrogen anion (hydrolysis, etc.) and carbene intermediates, and no efficient examples via radical intermediates were developed. Here, we reported a catalyst-free radical chain transformation of N-sulfonyl-1,2,3-triazoles to access an intermolecular oxidative C(sp3)-H coupling to yield N2-selective products in air without any catalysts.
RESUMEN
A simple and effective method for the synthesis of 3-aryl-3-substituted oxindole derivatives via a [Rh]-catalyzed three-component reaction of 3-diazooxindoles with N,N-disubstituted anilines and glyoxylates is developed. This transformation is proposed to proceed through an intermolecular aldol-type trapping of zwitterionic intermediates.