RESUMO
A one-pot tandem process was developed aiming at the concise and expeditious enantioselective synthesis of dihydrobenzofuran, dihydrobenzosulfone, and dihydroindole scaffolds under mild, and open-flask conditions. This process combines the inâ situ generation of aryldiazonium salt directly from the anilines in methanol telescoped to an intramolecular Heck-Matsuda reaction linked to a redox relay process to provide the final products as the dimethyl acetals. These Heck products were smoothly converted into the corresponding primary alcohols or esters. The robustness and the efficiency of the protocol are demonstrated by the synthesis of 24 enantioenriched dihydrobenzofurans, dihydrobenzosulfones, and dihydroindoles in overall yields up to 78 % in enantiomeric ratios up to 99 : 1 by a sequential 5-step protocol.
RESUMO
The trypanocidal activity of crude extracts and fractions from the leaves and stems of Peperomia obtusifolia (Piperaceae) was evaluated in vitro against the epimastigote forms of Trypanosoma cruzi. Bioactivity-guided fractionation of the most active extracts afforded seven known compounds, including three chromanes, two furofuran lignans and two flavone C-diglycosides. The most active compounds were the chromanes peperobtusin A and 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(2''-methyl-2''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2 H-1-benzopyran-6-carboxylic acid, with IC (50) values of 3.1 microM (almost three times more active than the positive control benznidazole, IC (50) 10.4 microM) and 27.0 microM, respectively. Cytotoxicity assays using peritoneal murine macrophages indicated that the chromanes were not toxic at the level of the IC (50) for trypanocidal activity. This is the first report on the trypanocidal activity besides unspecific cytotoxicity of chromanes from Peperomia species. Additionally it represents the first time isolation of 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(2''-methyl-2''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2 H-1-benzopyran-6-carboxylic acid from P. obtusifolia.
Assuntos
Cromanos/farmacologia , Peperomia/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Cromanos/isolamento & purificação , Estágios do Ciclo de Vida , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Nitroimidazóis/farmacologia , Fenóis/isolamento & purificação , Extratos Vegetais/química , Folhas de Planta , Caules de Planta , Tripanossomicidas/isolamento & purificaçãoRESUMO
Two highly oxygenated nortriterpenes, picraviane A and B, were isolated from the ethanolic extract of Picramnia glazioviana Engl. The structures were determined by analysis of HRMS and 2D NMR spectroscopic data. Single-crystal X-ray diffraction data was also obtained for picraviane B. The absolute configuration of both compounds were assigned by comparison of experimental and calculated vibrational and electronic circular dichroism spectroscopy, respectively. Picraviane A showed a moderate cytotoxic activity against the triple negative MDA-MB-231 breast cancer cell line. These compounds represent an undescribed class of natural products with limonoid-like skeletons containing a heptanolide as the E-ring.