RESUMO
BF3·Et2O-catalyzed double aldol condensation between acetylated steroid sapogenins and terephtalaldehyde led to acetylated dimeric spirostanols linked through a 1,4-dimethylidenebenzene moiety in moderate to good yields. The E configurations of the introduced double bonds were corroborated by NOE experiments. Saponification of the dimeric steroids led to the corresponding dimeric spirostanols.
Assuntos
Aldeídos/química , Benzeno/química , Boranos/química , Dimerização , Éter/química , Ácidos Ftálicos/química , Sapogeninas/química , Espirostanos/síntese química , Catálise , Técnicas de Química Sintética , Espirostanos/química , EstereoisomerismoRESUMO
Benzylidenespirostanols were prepared by two-step synthesis including BF3·Et2O-catalyzed aldol condensation of several acetylated steroid sapogenins with benzaldehyde followed by saponification. The obtained compounds showed moderate cytotoxicity against three cancer cell lines (T-lymphoblastic leukemia cell line CEM, breast carcinoma cell line MCF7 and cervical carcinoma cell line HeLa) and normal human fibroblasts (BJ). The most active of the five tested substances was 3c (lowest IC50 for MCF7 cells 19.9±0.1µM) without any selectivity towards human cancer and normal cells, respectively.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Sapogeninas/síntese química , Espirostanos/síntese química , Esteroides/síntese química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Sapogeninas/química , Sapogeninas/farmacologia , Espirostanos/química , Espirostanos/farmacologia , Esteroides/química , Esteroides/farmacologiaRESUMO
F-ring opening in spirostanes with the 16ß,22:22,25-diepoxy-23-acetoxymethyl-24-methyl side chain produces a Δ(22)-intermediate with an allylic acetoxy group. For this reason the reactivity profile of these compounds deviates from that observed in other naturally occurring or synthetic spirostanes and furospirostanes.
Assuntos
Compostos de Epóxi/síntese química , Espirostanos/síntese química , Catálise , Cristalografia por Raios X , Compostos de Epóxi/química , Halogenação , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Espirostanos/químicaRESUMO
The diversity-oriented synthesis of novel bis-spirostanic conjugates utilizing two different Ugi four-component reactions (Ugi-4CR) is described. Spirostanic steroids were functionalized with Ugi-reactive groups, that is, amines, isocyanides, and carboxylic acids, and next were subjected to multicomponent ligation approaches leading to bis-steroidal conjugates featuring pseudo-peptidic and heterocyclic linkage moieties. Both the classic Ugi-4CR and its hydrazoic acid variant were implemented, proving good efficiency for the ligation of isocyanosteroids to spirostanic acids and equatorial amines. Axially oriented amines showed poorer results, although model studies proved that chemical efficiency could be significantly improved while increasing reaction times. Overall, the method comprises the rapid generation of molecular diversity at the bis-steroid linkage moiety and, consequently, shows promise toward the production of combinatorial libraries of bis-spirostanes for biological screening.
Assuntos
Técnicas de Química Combinatória/métodos , Bibliotecas de Moléculas Pequenas/síntese química , Espirostanos/síntese química , Química Farmacêutica , Estrutura Molecular , Bibliotecas de Moléculas Pequenas/química , Espirostanos/química , EstereoisomerismoRESUMO
In addition to a previous report, the reaction of tigogenin acetate with ICl in refluxing CHCl(3) produced the hitherto unknown 23R-iodotigogenin acetate, bearing an axial iodine atom at C-23 and its already reported 23S-epimer. The same treatment of sarsasapogenin acetate led to a single diasteromer characterized as 23S-iodosarsasapogenin acetate. A full characterization of the obtained compound including (1)H, (13)C NMR, MS and X-ray diffraction is provided.
Assuntos
Iodo/química , Espirostanos/química , Espirostanos/síntese química , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , EstereoisomerismoRESUMO
Eight new 5beta-hydroxy-spirostan-6-ones bearing hydroxy and amino functions in the A ring, i.e., 3beta-OH, 3alpha-OH, 2beta,3beta-OH, 2alpha,3beta-OH, 3beta-NH2, 2alpha-NH2-3beta-OH, 2beta-NH2-3beta-OH, and 2beta-OH-3beta-NH2, were efficiently synthesized, and their antiecdysteroid activities were evaluated on the metamorphosis bioassay of mosquito Aedes aegypti. To our knowledge, these new steroids represent the first 5beta-hydroxy-spirostanes which have been tested for antiecdysteroid activity in mosquitoes. The higher antagonistic effect was found for compounds bearing the 3beta-hydroxy and 2beta,3beta-dihydroxy functionality, which show promise as environmental friendly insecticides.
Assuntos
Aedes/efeitos dos fármacos , Ecdisteroides/antagonistas & inibidores , Inseticidas/síntese química , Espirostanos/química , Espirostanos/síntese química , Animais , Inseticidas/farmacologia , Metamorfose Biológica/efeitos dos fármacos , Conformação Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The synthesis, spectroscopic characterization, and biologic activity of two bioactive spirostanic analogues of the naturally occurring brassinosteroid castasterone are described.