A concise effective deprotection of spiro 3-cyclic thiaza ketal of steroidal 1,4-dien-3-one

An effective deprotective method of spiro 3-cyclic thiaza ketal of steroidal 1,4-dien-3-ones using alkyl vinyl ether in the presence of protic acid followed by the treatment of aqueous alkali was described. This novel protocol could be fulfilled under mild condition with high yield. The mechanism mediated by a carbonium ion formed in situ was clarified by the capture of the cleaved fragment.     

Methandienone-I. A convenient method for the separation of 17alpha-methyl-17beta-hydroxyandrosta-i,4-dien-3-one and 17alpha-methyl-17beta-hydroxyanorosta-1,4,6-trien-3-one

17 α -Methyl-17 β -hydroxyandrosta-1,4-dien-3-one and 17α-methyl-17β-hydroxyandrosta-1,4, 6-trienone are found in the mother liquor of the reaction leading to the formation of the former from 17 α -methyl-17β -hydroxyandrosta-4-ene-3-one (I). This mother liquor usually discarded as waste product in the industrial production of 17α -methyl-17β -hydroxyandrosta-1,4-dien-3-one, can now be used for obtaining the two compounds separately using sodium metabisulfite.     

Total synthesis of heterocyclic steroids,part VII. Synthesis of (±)-8,13-diaza-3-thia-A-norgona-1,5(10)-dien-17-one

The total synthesis of (±)-8,13-diaza-3-thia-A-norgona-1,5(10)-dien-17-one (XII) was achieved starting from 2-(2-thienyl) ethylamine (VII) and 3-succinimidopropionyl chloride (IX) as the A and D ring precursors respectively.     

Practical one-pot conversion of 17beta-estradiol to 10beta-hydroxy- (p-quinol) and 10beta-chloro-17beta-hydroxyestra-1,4-dien-3-one

An efficient one-pot procedure for the preparation of 10beta,17beta-dihydroxyestra-1,4-dien-3-one (p-quinol, 1, 75%) is reported, involving oxidation of 17beta-estradiol with potassium permanganate. Similar treatment of 17beta-estradiol with sodium chlorite led to 10beta-chloro-17beta-hydroxyestra-1,4-dien-3-one (2) in 44% yield along with smaller amounts 4-chloro-10beta,17beta-dihydroxyestra-1,4-dien-3-one (3), 2,10beta-dichloro-17beta-hydroxyestra-1,4-dien-3-one (4), and 4,10beta-dichloro-17beta-hydroxyestra-1,4-dien-3-one (5).     

Effect of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one on reproductive organs of the male laboratory mouse

The effect of subcutaneous administration (10, 15 and 20 mg/kg body weight/day, for 21 days; and 20 mg/kg body weight/day, for 28 days) of 17 alpha-cyanomethyl-17 beta-hydroxy- estra-4, 9-dien-3-one (STS 557) on the male reproductive organs of the Parkes strain mouse was investigated. The effect of the treatment on the testis was not uniform; both regressed and normal seminiferous tubules were observed in the same section of the organ. Furthermore, the histological changes observed in the seminiferous tubules in testes of STS 557--treated mice were not different in different dosage groups. In general, in moderately affected seminiferous tubules, the germinal epithelium was thin and consisted of Sertoli cells, spermatogonia, spermatocytes and spermatids; such tubules showed presence of many vacuoles in the epithelium. In severe cases, the tubules had collapsed and were lined by mainly Sertoli cells, spermatogonia and spermatocytes. The treatment also caused marked depression in motility and concentration of spermatozoa in cauda epididymidis, weight of accessory sex glands and in the levels of sialic acid and fructose in the epididymis and seminal vesicle, respectively. By 56 days of drug withdrawal, the alterations induced in the reproductive organs returned to control levels, suggesting that STS 557 treatment induces reversible alterations in the male reproductive organs of Parkes strain mouse.     

Synthesis of 3-methoxy-5,6-secoestra-1,3,5(10),8,14-pentaen-17-one

A facile synthesis of 3-methoxy-5,6-secoestra-1, 3,5(10),8,14-pentaen-17-one from the readily available p-anisaldehyde is reported.     

Synthesis and testing of 17a beta-hydroxy-7 alpha-methyl-D-homoestra-4,16-dien-3-one: a highly potent orally active androgen

The title compound, 17a beta-hydroxy-7 alpha-methyl-D-homoestra-4,16-dien-3-one (3), was synthesized in five steps (17% overall yield) from 7 alpha-methylestrone methyl ether (5) and was found to possess oral androgenic activity, in excess of other known androgens, without using 17 alpha-alkyl substitution.     

Disposition and metabolism of 16 beta-ethyl-17 beta-hydroxy-4-estern-3-one (TSAA-291), a new antiandrogen, in rats.

Matabolic fate of a new antiandrogen, 16 beta-ethyl-17 beta-hydroxy-4-estren-3-one (TSAA-291), was studied in rats. 14C-TSAA-291 intramuscularly injected as an aqueous suspension was absorbed gradually to give an increase in the plasma level which attained a plateau at 0.5 h, persisted till 8 h and then declined with an approx. half-life of 3.6 days. The drug was widely distributed in tissues, with the concns. almost equal to or higher than that in the plasma. The 14C-drug was eliminated mostly as metabolites within 10 days after dosing with higher activities found in the feces than in urine. Biliary 14C effectively underwent enterohepatic cycling. Biliary metabolites of TSAA-291 were characterized by the combined use of deuterium labeling and GLC-MS analysis. The metabolites identified were as follows: the parent drug, monohydroxy TSAA-291 having the additional hydroxy function in the steroid skeleton, 17 beta-hydroxy-16 beta-(1 xi-hydroxyethyl)-4-estren-3-one, 16 beta-ethyl-17 beta-hydroxy-5 beta-estran-3-one, 16 beta-ethyl-17 beta-hydroxy-5 alpha-estran-3-one, 16 beta-ethyl-5 beta-estrane-3 alpha, 17 beta-diol, 16 beta-ethyl-5 alpha-estrane-3 alpha, 17 beta-diol, 16 beta-ethyl-3 alpha-hydroxy-5 beta-estran-17-one and 16 beta-ethyl-3 alpha-hydroxy-5 alpha-estran-17-one. Monoketodihydroxy and/or trihydroxy metabolites were also detected in the bile.     

Poly(ethylene oxide), a new slowing agent for protozoa.

The water-soluble, viscoelastic resin Polyox WSR 301), a poly(ethylene oxide) of high molecular weight (approximately 4 million) is introduces as a new slowing agent for protozoa. Generally, as the kinetic viscosity of the resin increased from 0.25% to 1% (w/v), the swimming velocity of Euglena gracilis, Didnium nasutum, Paramecium aurelia, Blepharisma undulans, and Prorodon platyodon decreased. The 1.0% solution had the highest viscosity and decreased velocity more effectively than 1.0% methyl cellulose and Protoslo solutions. The Polyox solutions differed from those of methyl cellulose and Protoslo by having, in addition to viscous drag, an elastic recoil that pulled the protozoa backwards when their swimming efforts stopped. The toxicity of these slowing agents was determined using 10 P. aurelia/test slide preparation. Paramecium numbers decreased in 1.0% methyl cellulose and Protoslo to nearly zero by 24 hr; in Polyox, not only were most these ciliates alive after 24 hr, but many survived for 96 hr and divisions occurred in 0.25% and 0.50% solutions.     

一个戊二烯酮化合物的合成及其杀菌抗癌活性

目的:合成戊二烯酮类化合物(1E,4E)-1,5-二(2-羟基苯基)-1 ,4-戊二烯-3-酮,并进行杀菌和抗肿瘤活性测定.方法:水杨醛和丙酮反 应得到目标产物;采用生长速率法和MTT比色法分别测定了该化合物的杀菌抗癌活性.结果:目标物结构经元素分析、红外光谱、核磁共振氢谱确证;该化合物在500 μg/mL浓度下对小麦赤霉病原菌、辣椒枯萎病原菌、苹果腐烂病原菌的抑制率分别为73.0% ±3.3%、70.4%±1.5%、79.2%±2.1%;在5.0ìmol/L下对PC-3细胞的72h的体外抑制率为71 .4%±2.7%.结论:该化合物有较好的杀菌抗癌活性,可以以它为先导进行结构优化,以期设计、合成出高效、选择性好的同类化合物.     

An approach to the mechanism of the potent antiglucocorticoid: 17 beta-hydroxy-11 beta-4-dimethylaminophenyl-17 alpha-propynyl-estra-4,9-dien-3-one

The effects of a new synthetic steroid, 17 beta-hydroxy-11 beta-4-dimethyl-aminophenyl-17 alpha-propynyl-estra-4,9-dien-3-one, classified under reference R38486 in the Roussel-Uclaf nomenclature [1], were investigated in two established rat hepatoma cell lines in order to gain information on the mechanism of action. The induction of tyrosine aminotransferase (TAT) and alanine aminotransferase (AAT) was totally abolished when R38486 was added with dexamethasone either on a 1-1 basis or on a 10-fold excess depending on the differentiation state of the cell. Binding studies showed a high affinity for the glucocorticoid receptor; however our "whole cell" study with [3H] R38486 indicates that only a low amount of antagonist-receptor complexes was translocated into the nucleus. Nuclear fractionation experiments showed that R38486, like the other antagonists studied, was located in the chromatin fraction where it may exert some definite role. Our observations based on whole cell experiments using physiological doses of glucocorticoid analogs indicate that the binding of activated antiglucocorticoid-receptor complexes to nuclear acceptor sites represents a physiologically significant process. Moreover the differences in the nuclear binding of antagonist-receptor- as compared to agonist-receptor-complexes may set off the machinery of antagonistic action.     

Heterocyclic steroids-part-VI: Studies on the total syntheses of racemic A-nor-3-thiaestra-1,5(10),6,8,14-pentaen-17(e)-OL and A-nor-3-thiaestra-1,5(10),8,14-tetraen-17(e)-OL

4-Oxo-4,5,6,7-tetrahydrothianaphthene(I) is converted into racemic A-nor-3-thiaestra-1,5(10),6,8,14-pentaen-17(e)-01(IX) and A-nor-3-thiaestra-1,5(10),8,14-tetraen-17(e)-01 (VIII).     

The identification of 14 alpha,17 beta-dihydroxyandrost-4-en-3-one monohydrate and 14 alpha,17 beta-dihydroxyandrosta-1,4-dien-3-one monohydrate, metabolites of androstenedione in Mucor piriformis.

The microorganism Mucor piriformis transforms androst-4-ene-3,17-dione into a major and several minor metabolites. X-ray crystallographic analysis of two of these metabolites was undertaken to determine unambiguously their composition and chirality. Crystals belong to the orthorhombic space-group P2(1)2(1)2(1), with a = 7.199(4) A and a = 6.023(3) A, b = 11.719(3) A and b = 13.455(4) A, c = 20.409(3) A and c = 20.702(4) A for the two title compounds, respectively. The structures have been refined to final R values of 0.060 and 0.040, respectively.