RESUMO
Conioidine A (1), isolated in 1993 with unknown relative and absolute configuration, was suggested to be a DNA-binding compound by an indirect technique. Four stereoisomers of conioidine A have been synthesized from d- and l-proline, and the natural product has been identified as possessing (4R,6R) absolute configuration. Binding of the conioidine diastereomers to calf thymus DNA (CT DNA) and human serum albumin (HSA) has been investigated by fluorescence spectroscopy and isothermal titration calorimetry (ITC). All stereoisomers display at least an order of magnitude weaker binding to DNA than the control compound netropsin; however, a strong association with HSA was observed for the (4R,6S) stereoisomer.
Assuntos
Pirrolidinas/química , Pirrolidinas/síntese química , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/síntese química , Sítios de Ligação , Ligação Competitiva/efeitos dos fármacos , Calorimetria , Dicroísmo Circular , DNA/química , Etídio , Simulação de Acoplamento Molecular , Estrutura Molecular , Netropsina/química , Netropsina/metabolismo , Prolina/química , Albumina Sérica Humana/química , Espectrometria de Fluorescência , EstereoisomerismoRESUMO
Concise total syntheses of the anthracenone C-glycosides alvaradoins E and F, uveoside, and 10-epi-uveoside (1-4) have been accomplished from chrysophanic acid 8 and bromosugar 9. Key steps in the syntheses include the DBU-induced coupling of 8 and 9 to produce ß-C-glycoside 11, and a Pb(OAc)4-mediated Kochi reaction to introduce the C-1' oxygen atom of the natural products. Isothermal titration calorimetry and fluorescence binding studies reveal that compounds 1 and 2 have good affinity for the plasma protein HSA.
