RESUMO
The synthesis and biological evaluation of three new cholestane frameworks of the type: (25R)-3ß,16ß-Diacetoxy-23-ethylidene-26-hydroxy-22-oxocholestane, starting from spirostanic sapogenins of the 25R series, is described. The compounds were obtained by the reductive cleavage of the F ring of 22-oxo-23(1),26-epoxycholestane derivatives using 9-BBN. These modified derivatives exhibit cytotoxic activity against CEM and MCF7 cells and are able to induce apoptosis in them. Its effect on the cell cycle was determined.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Colestanos/síntese química , Colestanos/farmacologia , Sapogeninas/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Técnicas de Química Sintética , Colestanos/química , HumanosRESUMO
The E ring regioselective acid-catalyzed opening of spirostanic sapogenins possessing a carbonyl group at C-12, such as botogenin and hecogenin, provided the new 12,23-cyclo-22,26-epoxycholesta-11,22-diene skeleton, in addition to new compounds of the already known 12,23-cyclocholest-12(23)-en-22-one frameworks. This transformation proceeds in a single step, under slightly acidic conditions. Both, penta- and hexacyclic steroids were obtained with retention of configuration of all asymmetric centers.
Assuntos
Sapogeninas/química , Sapogeninas/síntese química , Catálise , Análise Espectral , Compostos de Espiro/química , Estereoisomerismo , Esteroides/química , Especificidade por SubstratoRESUMO
A number of unexpected reactions were observed during attempts to invert configuration at C16 in 16alpha,17alpha,22-triol 3a. The PDC oxidation of 3a produced the D-seco-aldehyde 4a. Analogous compound 4b was obtained by Swern oxidation of the 16alpha,17alpha-dihydroxy-22-O-TES-ether 3b in addition to the desired 16-ketone 7. The unprotected triol 3a yielded pentacyclic products 5 and 6 under similar conditions. The Mitsunobu reaction of the triol 3a afforded 16-ketone 8 with inverted configuration of the side chain. During heating of a solution of 3a in THF with NaH at reflux autoxidation to the 16-ketone cyclic hemiketal 5, identical to one of the Swern oxidation products, took place.
