RESUMO
Treatment of steroid sapogenins with H2O2 in CF3COOH for 15min followed by reflux in CH3OH/H2O afforded good yields of pregnan-3ß,16ß,20-triol 3-monoacetates. When the hydrolysis step was carried out with KOH in refluxing methanol excellent yields pregnantriols were obtained. The resulting compounds were characterized by their melting points and NMR spectral data. An X-ray diffraction analysis of compound 3a confirmed the proposed structure and provided detailed information about the bond lengths, bond angles and conformation.
Assuntos
Pregnanolona/química , Sapogeninas/química , Esteroides/química , Cristalografia por Raios X , Peróxido de Hidrogênio/química , Hidrólise , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Sapogeninas/síntese química , Estereoisomerismo , Esteroides/síntese química , Temperatura de TransiçãoRESUMO
Neuroactive steroids, like allopregnanolone (A) and pregnanolone (P), bind to specifics sites on the GABAA receptor complex and modulate receptor function. They are capable to inhibit or stimulate the binding of GABAA receptor-specific ligands, like t-butyl-bicyclophosphorothionate, flunitrazepam and muscimol. We have previously characterized a set of oxygen-bridged synthetic steroids (SS) analogs to A or P using synaptosomes. Considering that the subunit composition of the GABAA receptor throughout the central nervous system affects the magnitude of the modulation of the GABAA receptor by NAS, we evaluated the action of two selected SS, in brain sections containing the cerebral cortex (CC) and hippocampus (HC) using quantitative receptor autoradiography. Both SS affected the binding of the three ligands in a similar way to A and P, with some differences on certain CC layers according to the ligand used. One of the SS, the 3α-hydroxy-6,19-epoxypregn-4-ene-20-one (compound 5), behaved similarly to the natural neuroactive steroids. However, significant differences with compound 5 were observed on the HC CA2 region, making it steroid suitable for a specific action. Those differences may be related to structural conformation of the SS and the subunits' composition present on the receptor complex.
Assuntos
Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Pregnanolona/análogos & derivados , Receptores de GABA-A/metabolismo , Animais , Autorradiografia , Ligação Competitiva , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Córtex Cerebral/efeitos dos fármacos , Flunitrazepam/metabolismo , Agonistas de Receptores de GABA-A/metabolismo , Agonistas de Receptores de GABA-A/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Muscimol/metabolismo , Pregnanolona/química , Pregnanolona/metabolismo , Pregnanolona/farmacologia , Ligação Proteica , Ratos Sprague-Dawley , Radioisótopos de Enxofre , TrítioRESUMO
Two new terpenoids, ambrosanoli-10(14)-en-11,12-diol (1), a sesquiterpene named quadrijugol, and a pregnane steroid, 3beta,4beta-dihydroxypregnan-16-one (2), were isolated from the stem and leaves of Trichilia quadrijuga, along with eleven known compounds, spathulenol, kudtdiol, 2beta,3beta,4beta-trihydroxypregnan-16-one, bourjotinolone B, piscidinol, niloticin, dihydroniloticin, beta-sitosterol, 3-O-beta-D-glucopyranosyl-sitosterol, itesmol and stigmasterol. Structures were elucidated by spectral data analysis, mainly afforded by 1H and 3C NMR (1D and 2D NMR HMQC, HMBC, NOESY and COSY) and mass spectra.