RESUMEN
Synthesis of 21,22-cyclosteroids has been achieved starting from pregnenolone acetate. The key transformation was the Kulinkovich reaction of 17-vinyl steroids with esters. The resulting cyclopropanols were further subjected to three-membered ring-opening under various conditions including to base-, palladium or visible light-promoted isomerization and cross-coupling reaction. A number of steroidal Δ2-6-ketones and 3ß-hydroxy-Δ5-enes with functional groups at C-21 - C-23 have been synthesized via the 21,22-cyclosteroids. The antiproliferative and antihormonal activity of the obtained compounds on the cell lines of prostate (22Rv1) and breast (MCF-7) cancer was studied. The androgen receptor activity was assessed by reporter assay when the expression of signalling proteins was evaluated by immunoblotting. (20S,22R)-22-Acetoxy-21,22-cyclo-5α-cholest-5-ene with the moderate antiandrogenic potency revealed IC50 values of 18.4 ± 1.2 and 14.6 ± 1.4 µM against MCF-7 and 22Rv1 cells, respectively, and its effects on the expression of AR-V7, cyclin D1 and BCL2 were explored.
Asunto(s)
Antineoplásicos , Cicloesteroides , Humanos , Masculino , Línea Celular Tumoral , Proliferación Celular , Cicloesteroides/química , Cicloesteroides/farmacología , Imidazoles , Pregnenolona , Receptores Androgénicos/metabolismo , Esteroides , Neoplasias de la Mama/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologíaRESUMEN
The BF3·Et2O-promoted reaction of 3ß-acetoxy-5,19-cyclo-pregnan-6ß-ol-20-one with different nucleophiles was investigated. B-homo steroids (3ß-acetoxy-B-homo-6a-ß-alkoxy-pregna-5(10)-en-20-ones) were obtained with primary and secondary alcohols, while the reaction with common carboxylic acids selectively afforded the corresponding 3ß-acetoxy-6ß-(acyloxymethyl)-pregna-5(10)-en-20-ones. The transformations are supposed to proceed via the rearrangement of a cyclopropyl-methyl cation (bicyclobutonium) intermediate, which is regioselectively opened in dependence on the nucleophile employed. The method represents an efficient, diversity-oriented entry to new B-ring-modified steroids, which are of potential pharmaceutical relevance.
Asunto(s)
Boranos/química , Cicloesteroides/síntesis química , Pregnenolona/química , Esteroides/química , Ácidos Carboxílicos/química , Cicloesteroides/química , Estructura MolecularRESUMEN
Cyclosteroidal "cholaphane" anion transporters show increased activities compared to acyclic "cholapod" analogues.
Asunto(s)
Aniones/metabolismo , Cicloesteroides/química , Sitios de Unión , Transporte Iónico , Modelos MolecularesRESUMEN
Six new polyhydroxylated steroidal saponins, tupistrosides A-F (1-6), together with nine known steroids, were isolated from the fresh rhizomes of Tupistra yunnanensis. Their structures were elucidated to be (25S)-1beta,4beta,5beta-trihydroxy-spirostane-3beta-yl O-alpha-l-arabinopyranoside (1), 1beta,24beta-dihydroxy-spirost-5,25(27)-dien-3alpha-yl O-beta-d-glucopyranoside (2), (22S,25S)-1alpha,2beta,3alpha,5alpha-tetrahydroxy-furo-spirostane-26-yl O-beta-d-glucopyranoside (3), 1beta,3alpha,22 xi-trihydroxy-furost-5,25(27)-dien-26-yl O-beta-d-glucopyranoside (4), 26-O-beta-d-glucopyranosyl-1beta,22-dihydroxy-furost-5-en-3alpha-yl O-beta-d-glucopyranoside (5) and 22-methoxy-1beta,2beta,3beta,4beta,5beta,7alpha-hexahydroxy-furost-25(27)-en-6-one-26-yl O-beta-d-glucopyranoside (6), respectively, by means of spectroscopic analysis and the results of acid hydrolysis.
Asunto(s)
Cicloesteroides/aislamiento & purificación , Liliaceae/química , Extractos Vegetales/aislamiento & purificación , Rizoma/química , Saponinas/aislamiento & purificación , Ácido Clorhídrico , Hidrólisis , Estructura Molecular , Saponinas/análisisRESUMEN
Further search for steroidal compounds contained in Dracaena surculosa (Agavaceae) led to the isolation of two new 3,5-cyclospirostanol saponins (1, 2) and two new 3,5-cyclofurostanol saponins (3, 4). Their structural assignment was established by spectroscopic analysis and a few chemical transformations as (24S,25R)-1beta-[(beta-D-fucopyranosyl)oxy]-6beta-hydroxy-3alpha,5alpha-cyclospirostan-24-yl beta-D-glucopyranoside (1), (24S,25R)-1beta-[(beta-D-glucopyranosyl)oxy]-6beta-hydroxy-3alpha,5alpha-cyclospirostan-24-yl beta-D-glucopyranoside (2), (25S)-1beta-[(beta-D-glucopyranosyl)oxy]-6beta-hydroxy-22alpha-methoxy-3alpha,5alpha-cyclofurostan-26-yl beta-D-glucopyranoside (3), and (25S)-1beta-[(beta-D-fucopyranosyl)oxy]-6beta-hydroxy-22alpha-methoxy-3alpha,5alpha-cyclofurostan-26-yl beta-D-glucopyranoside (4), respectively.
Asunto(s)
Cicloesteroides/química , Dracaena/química , Saponinas/química , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Metanol , Modelos Moleculares , Extractos Vegetales/química , Solventes , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
The ring contraction of 18 alpha-mesyloxy-20 alpha-hydroxy-18,20-cyclopregn-4-en-3-one (Ib) and 18 alpha-mesyloxy-20 alpha-hydroxy-21-acetyloxy-18,20-cyclo-pregn-4-en-3-one (Id) took place upon exposure to Florisil at 25 degrees C, producing 18 alpha-acetyl-17,18-cycloandrost-4-en-3-one (IIa) and 18 alpha-acetoxyacetyl-17,18-cycloandrost-4-en-3-one (IIb) respectively. A similar ring contraction of 18 alpha, 20 alpha-dihydroxy-18,20-cyclopregn-4-en-3-one (Ia) took place upon electron impact. Deuterium labeling demonstrated that the first steps of mass spectral fragmentation of Ia were the rearrangement to IIa and the oxidative cleavage to 3,18,20-trioxo-4-pregnene (IVa).
Asunto(s)
Androstenos/síntesis química , Cicloesteroides/síntesis química , Androstenos/metabolismo , Animales , Cicloesteroides/metabolismo , Femenino , Riñón/metabolismo , Espectrometría de Masas , Conejos , Ratas , Receptores de Esteroides/metabolismo , Útero/metabolismoAsunto(s)
Antagonistas de Andrógenos , Homoesteroides/farmacología , Congéneres de la Testosterona , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Animales , Cicloesteroides/farmacología , Citosol/metabolismo , Dihidrotestosterona/metabolismo , Técnicas In Vitro , Masculino , Próstata/metabolismo , Ratas , Receptores Androgénicos/metabolismo , Vesículas Seminales/efectos de los fármacos , Globulina de Unión a Hormona Sexual/metabolismo , Esteroides/metabolismo , Relación Estructura-ActividadRESUMEN
An improved procedure for the isolateion suprasterol2 I and II from a photochemical reaction mixture of ergocalciferol (vitamin D2) and their spectral data are described in this paper. When a solution of ergocalciferol in ethanol was irradiated by UV light from a high-pressure mercury lamp, the reaction mixture gave six spots, including suprasterol2 I and II, on the thin-layer chromatogram, while the peaks corresponding to pyro-D2, isopyro-D2,5,b-trans-D2, suprasterol 2 I and II were observed in the gas chromatogram obtained from a capillary column GLC (Suprasterol2 I and II were main peaks). After purifying the mixture by column chromatography on silica gel containing 12% alumina as an absorbent, two main fractins were isolated. The data of their spectra, TLC and GLC showed that the former fraction was suprasterol2 II while the latter was suprasterol2 I and that the both fractions contained the respective compound only. Both suprasterol2 were crystallized as the 3,5-dinitro-benzoates.
Asunto(s)
Ergocalciferoles/efectos de la radiación , Esteroles/aislamiento & purificación , Rayos Ultravioleta , Cicloesteroides/análisis , Cicloesteroides/aislamiento & purificación , Esteroles/análisisAsunto(s)
Cicloesteroides , Alquinos , Colestanonas , Cetosteroides , Naftalenos , Oxidación-Reducción , Secoesteroides , SolventesRESUMEN
The neutral urinary excretion products of 17beta-hydroxy-2alpha, 3alpha-cyclopropano-5alpha-androstane from the rabbit, dosed orally, were investigated. Column chromatography yielded five crystalline metabolites which were identified by GLC and spectroscopic measurements. Three of these substances were hydroxylated in the 4alpha-position and one in the 6alpha-position with the cyclopropane ring intact. The fifth substance, 17beta-hydroxy-3beta-methyl-5alpha-androstan-2-one, can be derived from initial hydroxylation of the cyclopropane ring at C-2 followed by ring opening. The dosed substance and triol material was shown to be present by GLC and m.s. measurements. GLC determinations show that hydroxylation has occurred at C-4-C-6-C-2.
Asunto(s)
Androstanos/metabolismo , Androstanos/orina , Animales , Cromatografía de Gases , Cicloesteroides/metabolismo , Hidroxilación , Espectroscopía de Resonancia Magnética , Conejos , Espectrofotometría InfrarrojaRESUMEN
Two different synthetic routes have been used to synthesize a series of cyclopropyl conjugated ketones in which 4alpha,6-unsaturation replaces the usual 4,5-unsaturation. The synthetic routes involve intramolecular ketocarbene addition to a 5-6 double bond and intramolecular 1,3-elimination of 6beta-substituted 5beta-3-keto steroids. Both routes give 5beta products. The analogs of progesterone, testoterone acetate, and norethisterone have been prepared and shown to be remarkably biologically inactive when compared with the corresponding standard. Possible reasons for such inactivity are discussed.