- Microwave-assisted stereoselective approach to novel steroidal ring D-fused 2-pyrazolines and an evaluation of their cell-growth inhibitory effects in vitro
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Novel ring D-condensed 2-pyrazolines in the Δ5-androstene series were efficiently synthesized from 16-dehydropregnenolone or its acetate with different arylhydrazines or methylhydrazine, respectively, under microwave irradiation. The reactions are assumed to occur via hydrazone intermediates, followed by intramolecular 1,4-addition leading to the fused heteroring stereoselectively with a 16α,17α-cis ring junction. The synthesized compounds were subjected to in vitro pharmacological studies of their antiproliferative activities against four human breast (MCF7, T47D, MDA-MB-231 and MDA-MB-361) and three cervical (HeLa, C33A and SiHA) malignant cell lines. Flow cytometry revealed that the most potent agent elicited a cell cycle disturbance.
- Mótyán, Gergo,Kovács, Ferenc,W?lfling, János,Gyovai, András,Zupkó, István,Frank, éva
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- Synthesis and characterization of new phenyl esters derived from 16-dehydropregnenolone acetate (16-DPA)
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A series of new phenyl esters based on a 5,16-pregnadiene-20-one skeleton, namely 3β-benzoyloxy-5,16-pregnadiene-20-ones, which may be good inhibitors of 17α-hydroxylase and 5α-reductase enzyme or useful intermediates for producing steroidal drugs, were synthesized starting from diosgenin. The structures of the steroids were characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, infrared (IR), and mass spectra.
- Li, Hongqi,Fang, Jueshu,Li, Juan,Wang, Yulong,Tian, Xiujuan,Xiang, Yuanhui
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- Allimacrosides A–E, new steroidal glycosides from Allium macrostemon Bunge
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A new pregnane-type steroidal glycoside (1), two new spirostane-type steroidal glycosides (2, 3), and two new furostane-type steroidal glycosides (4, 5), named allimacrosides A–E, together with four known compounds (6–9) were isolated from a 80% MeOH extract of Allium macrostemon Bunge. The identification and structural elucidation of these compounds were based on their 1D- and 2D-NMR spectra, and HR-FAB-MS data analysis. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using the sulforhodamine B bioassay.
- Kim, Yun Sik,Suh, Won Se,Park, Kyoung Jin,Choi, Sang Un,Lee, Kang Ro
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- Selective ring-opening carbonylation of epoxy-steroids
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Ring-opening alkoxycarbonylation of epoxy-steroids has been carried out with a Co2(CO)8/3-hydroxypyridine catalytic system. High chemo- and regioselectivities were obtained under the reaction conditions applied. Structural analysis of the products proved their high stereochemical purity in each case, accompanied by inversion of the original configuration. No carbonylation took place for sterically hindered steranic epoxides.
- Balazs, Attila,Benedek, Csilla,Szalontai, Gabor,Toroes, Szilard
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- Stereoselective syntheses of unnatural steroidal C(20R) aldehydes by ionic hydrogenation of C-20 tertiary alcohols
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Syntheses of three unnatural steroidal C(20R) aldehydes have been realised from 16-dehydropregnenolone acetate. The salient feature of the synthesis is the ionic hydrogenation of C-20 tertiary alcohols leading to the formation of the C(20R) unnatural isomer with complete stereoselectivity. Oxidative hydrolysis of the dithiane moiety furnished the C(20R) aldehydes.
- Shingate, Bapurao B.,Hazra, Braja G.,Pore, Vandana S.,Gonnade, Rajesh G.,Bhadbhade, Mohan M.
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- Stereoselective synthesis and antimicrobial activity of steroidal C-20 tertiary alcohols with thiazole/pyridine side chain
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Stereoselective synthesis of novel steroidal C-20 tertiary alcohols with thiazole and pyridine side chain using Grignard reaction of steroidal ketones and thiazole/pyridine magnesium bromide have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compounds exhibited significant antifungal and antibacterial activity against all the tested strains.
- Shingate, Bapurao B.,Hazra, Braja G.,Salunke, Deepak B.,Pore, Vandana S.,Shirazi, Fazal,Deshpande, Mukund V.
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- Synthesis and Identification of Pregnenolone Derivatives as Inhibitors of Isozymes of 5α-Reductase
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Hyperplasia of the prostate gland and prostate cancer have been associated with high levels of serum 5α-dihydrotestosterone. This steroid is formed from testosterone by the activity of the enzyme 5α-reductase (5α-R) present in the prostate. Thus, inhibition of this enzyme could be a goal for therapies to treat these diseases. This study reports the synthesis and effects of five different 21-esters of pregnenolone derivatives as inhibitors of 5α-R types 1 and 2. The activity of these steroidal compounds was determined using in vivo and in vitro experiments. The results indicate that of the five steroids studied, the 21(p-fluoro)benzoyloxypregna-4,16-diene-3,6,20-trione derivative, whose structure has not yet been reported, has the best molecular conformation to inhibit the in vitro activity of both types of 5α-R. In addition, this steroid also displayed activity in vivo. Apparently, its pharmacological effect was increased by the presence of a keto group at C-6, because this group decreased the possibility that the steroid would be metabolized by hepatic enzymes. In addition, the double bond present at C-4 of this compound also enhanced its inhibitory activity on 5α-R, and the C-21 ester moiety increased its liphophilicity. Therefore, its solubility in the cell membrane and its pharmacological activity were both increased.
- Chávez-Riveros, Alejandra,Bratoeff, Eugene,Heuze, Yvonne,Soriano, Juan,Moreno, Isabel,Sánchez-Márquez, Araceli,Cabeza, Marisa
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- Synthesis and evaluation of pyrimidine steroids as antiproliferative agents
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A small and focused library of steroidal non-fused and fused pyrimidines was prepared from pregnenolone acetate and diosgenin, respectively. The key step was the cycloaddition reaction of nitrogen-containing 1,3-binucleophiles with the steroidal α,β-unsaturated ketone. Urea, thiourea and guanidine reacted in a similar manner and afforded the steroidal pyrimidines in good yields. The antiproliferative tests against human tumor cell lines gave GI50 values in the micromolar range and had no effect on healthy fibroblasts. Additional experiments indicated that the compounds did not act as P-glycoprotein substrates, thus avoiding the rise of drug resistance. The fused steroidal pyrimidinethione was selected as drug lead for further testing due to its strong antiproliferative activities within the low micromolar range.
- Cortés-Percino, Alejandra,Vega-Báez, José Luis,Romero-López, Anabel,Puerta, Adrián,Merino-Montiel, Penélope,Meza-Reyes, Socorro,Padrón, José M.,Montiel-Smith, Sara
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- Design and synthesis of novel steroidal imidazoles as dual inhibitors of AR/CYP17 for the treatment of prostate cancer
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Both AR and CYP17 are important targets for blocking androgen signaling, and it has been accepted that multifunctional drugs have a low risk of drug resistance in the treatment of cancer. Thus, herein a series of steroidal imidazoles were designed, synthesized and evaluated as dual AR/CYP17 ligands. Several compounds displayed good biological profiles in both enzymatic and cellular assays. SAR studies showed that introducing oximino at the C-3 position of steroidal scaffold is beneficial to the enhancement of AR antagonistic activity. Among these compounds, the most potent compound 13a exhibited the best AR inhibition (IC50 = 0.5 μM) that was 27-fold increase compared with the hit compound 5 as well as comparable CYP17 inhibition (IC50 = 11 μM). Additionally, 13a displayed promising anti-proliferative effects on LNCap cell lines with the IC50 value of 23 μM which was superior to positive control Flutamide (IC50 = 28 μM). Furthermore, the docking results of 13a revealed that the oxygen atom at the position of C-3 connected to the heme of CYP17, which may be helpful for its satisfactory dual-target inhibition. In summary, this study provides an efficient strategy for multi-targeting drug discovery in the treatment of prostate cancer.
- Hou, Qiangqiang,He, Conghui,Lao, Kejing,Luo, Guoshun,You, Qidong,Xiang, Hua
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- Steroid-fullerene adducts from Diels-Alder reactions: Characterization and the effect on the activity of Ca2+-ATPase
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Two new fullerene steroids (1 and 6) have been prepared by the Diels-Alder reaction of silyloxydienes (2 and 3) with [60]fulterene, followed by hydrolysis of the silyl enol ether under acidic conditions. The isolation, characterization, UV-Vis and CD absorption studies of the adducts are presented. A preliminary study on the effect of 1 on sarcoplasmic reticulum (SR) Ca2+-ATPase and survival of human lung adenocarcinoma cancer A549 cells has also been carried out.
- Li, Lian-Sheng,Hu, Yun-Jin,Wu, Yikang,Wu, Yu-Lin,Yue, Jiachang,Yang, Fuyu
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- COSTUSOSIDE-I AND COSTUSOSIDE-J, TWO NEW FUROSTANOL SAPONINS FROM THE SEEDS OF COSTUS SPECIOSUS
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The structure of costusoside I and costusoside J have been established as 3-O-2)-α-L-rhamnopyranosyl (1-->2) 4)>-β-D-glucopyranosyl>-26-O-(β-D-glucopyranosyl-22α-methoxy-25R)-furost-5-en-3β,26-diol and its 22-hydroxy compound respectively, isolated from the seeds of Costus speciosus.Key Word Index - Costus speciosus; Costaceae; furostanol saponin; 3-O-2)-α-L-rhamnopyranosyl (1-->2) 4)>-β-D-glucopyranosyl>-26-O-(β-D-glucopyranosyl)-(25R)-furost-5-en-3β,22α,26- triol and its 22α-methoxy derivative.
- Singh, Sheo B.,Thakur, Raghunath S.
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- Reactivity of steroidal 1-azadienes toward enamines: an approach to novel chiral penta- And hexacyclic steroids
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The chemical behavior of steroidalN-sulfonyl-1-azadienes toward carbonyl compounds, in the presence of pyrrolidine, is described. With aldehydes, these azadienes participate in hetero-Diels-Alder reactions with thein situgenerated enamines. The stereoselectivity results from the approach of the dienophiles from the less hindered α-face of the steroid, with the pyrrolidine moietyendoand retention of the enaminetransgeometry. This diastereoselective synthetic methodology led to a new class of chiral pentacyclic steroids. Interestingly, the studied steroidal scaffolds follow a different mechanistic pathway with cyclic ketones. They undergo a diastereoselective annulation reaction, under enamine catalysis, affording chiral hexacyclic steroids.
- Lopes, Susana M. M.,Santos, Joana R. C.,Pinho e Melo, Teresa M. V. D.
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p. 1122 - 1132
(2021/02/16)
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- Synthesis and evaluation of some novel pregnane derivatives as anti-hyperlipidemic and anti-oxidant agents
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In the present paper, synthesis of few novel pregnane derivatives and their evaluation as potential anti-hyperlipidemic and anti-oxidant agents has been reported. The synthesis of 3β-hydroxy-16α-methoxy pregn-5-en-20-one (4) was achieved by reaction of 3β-hydroxy-5,16-pregnadiene-20-one (3) with KOH/MeOH under reflux. Compound 4 on treatment with succinic and phthalic anhydride afforded compound 6 and 7, respectively. The reaction of the C-20-oxime-pregnadiene (8) with 1,5-dibromohexane yielded 20-(O-6-bromo hexyl)-oximino-3β-hydroxy-pregn-5, 16-diene (9). A novel heterocyclic derivative 3β-hydroxy-androst-5-en [17,16-c]-2′-methyl-7′ bromo-3′,4′-dihydro quinoline (16) was synthesized by reaction of 3 with 3-bromoaniline. However, attempted synthesis of other heterocyclic derivatives by reaction of (3) with other halogenated amine led to Aza-Michael addition products (10-14). The synthesized compounds were also evaluated for their anti-hyperlipidemic and anti-oxidant activities. Compounds 6 and 14 were found to exhibit more lipid lowering and antioxidant activities in comparison to other compounds.
- Sethi, Arun,Bhatia, Akriti,Singh, Ranvijay Pratap,Srivastava, Atul
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- 20-triazole-20-hydroxyl-pregnane derivatives, method for preparing same and medical application of 20-triazole-20-hydroxyl-pregnane derivatives
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The invention belongs to the field of medicines, and particularly relates to a series of 20-triazole-20-hydroxyl-pregnane derivatives, a method for preparing the same and medical application of the 20-triazole-20-hydroxyl-pregnane derivatives. The 20-triazole-20-hydroxyl-pregnane derivatives are particularly used for preparing medicines for treating androgen receptor related diseases such as cellproliferation, prostate cancer, polytrichia, acne and androgenic alopecia which are dependent on androgens. Structural general formulas of compounds of the 20-triazole-20-hydroxyl-pregnane derivativesare shown. Details of definition of various groups in the general formulas are attached to specifications.
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Paragraph 0086; 0087; 0088; 0134; 0135; 0136
(2018/11/22)
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- Synthesis and anti-cancer activity of chiral tetrahydropyrazolo[1,5-a]pyridine-fused steroids
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Regio- and stereoselective synthesis of novel chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine–fused steroids via [8π?+?2π] cycloaddition of diazafulvenium methides with steroidal scaffolds is reported. The biological evaluation of the new family of hexacyclic steroids as anti-cancer agents was also carried out. Hexacyclic steroids bearing a benzyl group at C-22, derived from 16-dehydropregnenolone and 16-dehydroprogesterone, show considerable cytotoxicity against EL4 (murine T-lymphoma) in contrast with the corresponding C-22-unsubstituted derivatives showing low cytotoxicity. Thus, results indicate that the presence of the benzyl group is important to ensure cytotoxicity.
- Lopes, Susana M.M.,Sousa, Emanuel P.,Barreira, Luísa,Marques, Cátia,Rodrigues, Maria Jo?o,Pinho e Melo, Teresa M.V.D.
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- Steroidal androgen receptor inhibitor as well as preparation method and medical application thereof
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The invention relates to the field of medicinal chemistry, in particular relates to a steroidal androgen receptor inhibitor as well as a preparation method and medical application thereof, and particularly discloses medicines for treating related diseases of an androgen receptor, for example, cell proliferation dependent on androgen, hirsutism, acnes, androgenetic alopecia and the like. The general structural formula of the compound is as shown in the specification; and group definitions in the general formula are specified in the specification.
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Paragraph 0021; 0022; 0023; 0076; 0077; 0078; 0097-0099
(2016/12/26)
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- In order to double-ketene acetum acid ester as the raw material to synthesize the 16-pregnancy double alkene alcohol ketone method
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The invention discloses a method for synthesizing 16-dehydropregnenolone by taking dehydropregnenolone acetate as a raw material. The method comprises the following steps: dissolving dehydropregnenolone acetate by taking an aprotic solvent as a solvent, adding an aqueous solution of an inorganic base, controlling the reaction temperature to 20-30 DEG C, regulating the pH value to be neutral after the reaction is detected to be finished, raising the temperature to recover the solvent, performing atmospheric distillation and reduced pressure recovery, and adding water for filtering, wherein the filter cake is the 16-dehydropregnenolone. According to the method, protic solvents such as alcohols are avoided, hydrophilic aprotic solvents are used, a few byproducts are produced, and high-purity 16-dehydropregnenolone is obtained.
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Paragraph 0017; 0028-0030
(2017/05/16)
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- A practical solution for aqueous reactions of water-insoluble high-melting-point organic substrates
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A practical solution to the problem of performing aqueous reactions for very sparingly soluble high-melting-point (VSSHMP) organic substrates has been developed, which entails mechanically stirring a mixture of the substrate, the corresponding reagent(s), water, catalytic Aliquat 336 and sand. When the melting points of the substrates which include steroids, ketones, aldehydes, aromatics and alkaloids are around 200 °C, the reactions can be performed at 20 °C. The substrate solubility can be as low as 1 × 10-10 mol L-1. The Royal Society of Chemistry 2012.
- Cui, Xiaoxue,Li, Bo,Liu, Tianzhen,Li, Chunbao
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supporting information; experimental part
p. 668 - 672
(2012/06/01)
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- Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
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The lipophilic nature of allopregnanolone prevents its user-friendly application in human medicine. On inspiration by pReviously prepared allopregnanolone with a 16α -bound tetraethylammonium salt, an attempt was made to produce allopregnanolone analogues
- Slavíková, Barbora,Kri?tofíková, Zdena,Chodounská, Hana,Budě?ínsky, Milo?,Durán, Fernando J.,Veleiro, Adriana S.,Burton, Gerardo,Kasal, Alexander
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experimental part
p. 2119 - 2125
(2009/12/31)
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- Highly efficient epoxidation of unsaturated steroids using magnesium bis(monoperoxyphthalate) hexahydrate
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Fast generation of epoxides from the corresponding homoallylic and allylic steroidal olefins was developed by using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) as oxidant suspended in acetonitrile (CH3CN) at reflux temperature. The protocol involves the use of a safe readily available oxidant along with an easy work-up, which renders the process very efficient. Selective 4,5- and 5,6-epoxidations of steroids are reported. Among them, highly stereoselective epoxidation of Δ5-B-nor-cholestanes was achieved. Moreover, the method is chemoselective for the 5,6-position and can be applied to the epoxidation of ring-A enones.
- Carvalho, Jo?o F.S.,Silva, M. Manuel Cruz,Sá e Melo, M. Luisa
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experimental part
p. 2773 - 2781
(2009/08/15)
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- KHSO4-SiO2-MeOH An efficient selective solid-supported system for deprotection of alcohols from esters
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KHSO4-SiO2 can efficiently deprotect alcohols from esters through transesterification in methanol under mild condition. Esters of aromatic alcohols are easily transesterified at room temperature compared to the corresponding aliphatic or alicyclic alcohol. NAcetyl compounds and ethers are resistant to the reagent under the above condition. The method is very useful for preparation of biodiesel methyl ricinoleate from castor oil.
- Goswami, Amrit,Das, Ram N.,Borthakur, Naleen
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p. 1893 - 1895
(2008/09/19)
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- Stereoselective syntheses of 20-epi cholanic acid derivatives from 16-dehydropregnenolone acetate
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A stereoselective total synthesis of naturally occurring 20-epi cholanic acid derivatives has been realized, starting from readily available 16-dehydropregnenolone acetate. The key step of these syntheses involves an ionic hydrogenation of a C-20,22-ketene dithioacetal and deoxygenation of steroidal C-20 tert-alcohols, to set up the unnatural C(20R) configuration with 100% stereoselectivity. The unnatural C-22 aldehydes with C(20R) stereocenters thus obtained were elaborated to 20-epi cholanic acid derivatives. Two derivatives of 20-epi cholanic acid were synthesized and their structures have been confirmed by single crystal X-ray analysis. Catalytic hydrogenation of 16-dehydropregnenolone acetate and 16-dehydropregnenolone in ethanol affords C-5,C-16 tetrahydro products. Crystal structure analysis of one of these products revealed C-5α and C-17α configurations of the hydrogen atoms.
- Shingate, Bapurao B.,Hazra, Braja G.,Pore, Vandana S.,Gonnade, Rajesh G.,Bhadbhade, Mohan?M.
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p. 5622 - 5635
(2008/01/06)
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- Mild and selective deprotection method of acetylated steroids and diterpenes by dibutyltin oxide
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Dibutyltin oxide (DBTO) was first utilized for the deacetylation of steroid and diterpene esters. The results showed the deprotection of acetylated steroids and diterpenes separately with moderate catalysis dibutyltin oxide in methanol selectively removed part acetyl groups of these substrates, whereas several functional groups of the steroids and diterpenes were retained and neither isomerization nor degradation of these substrates was observed. It seems that the acetyl groups with lower steric hindrance or near carbonyl, alkoxy, or hydroxyl groups can be cleaved by the reaction, whereas the acetyl groups with higher steric hindrance or without carbonyl, alkoxy, or hydroxyl groups neighboring were retained under the same conditions. One of the interesting results obtained was the selective hydrolysis of the 3β-O-acetyl group in the presence of the 6β group in 3β,6β-Di-O-acetyl-5α-hydroxypregn-16-en-20-one. This allows for subsequent introduction of one unit at C-3 and the other unit at C-6. This procedure is useful for the synthesis of a series of closely related isomers of 3β,5α,6β-trihydroxypregn-16-en-20-one and other widespread polyhydroxysteroids in marine organisms and some terrestrial species.
- Wang, Shao-Min,Zhang, Yan-Bing,Liu, Hong-Min,Yu, Guo-Bin,Wang, Ke-Rang
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- Expeditious and convenient synthesis of pregnanes and its glycosides as potential anti-dyslipidemic and anti-oxidant agents
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A series of new pregnane derivatives and its glycosides were synthesized in order to find new 'leads' against some important targets. The 3β-hydroxy-16α-(2-hydroxy ethoxy) pregn-5-en-20-one (5) was synthesized from 3β-hydroxy-5,16-pregnadiene-20-one (2) by adopting general modified procedure using BF3:Et2O as a catalyst. Reduction of 5, with sodium borohydride yielded 3β,20β-dihydroxy-16α-(2-hydroxy ethoxy) pregn-5-en (7) as the major isolable product. O-alkylation of the C-20-oxime-pregnadiene (9) with 1,5-dibromopentane yielded 20-(O-5-bromopentyl)-oximino-3β-hydroxy-pregn-5,16-diene (11). Synthesis of C-16 substituted pregnane glycosides (20) and (21) were accomplished with the imidate method using BF3:Et2O. The synthesis of 4-chlorobenzoate (3) and 2-chlorobenzoate (4), derivatives of 2 were also accomplished. These compounds were evaluated for their anti-dyslipidemic and anti-oxidant activity and amongst them compounds 3 and 7 showed more lipid lowering and anti-oxidant activity.
- Sethi, Arun,Maurya, Atul,Tewari, Vibha,Srivastava, Sanjay,Faridi, Shaheen,Bhatia, Gitika,Khan,Khanna,Saxena
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p. 4520 - 4527
(2008/03/13)
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- Production process for 16-dehydropregnenoneol and its analogs
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The present invention relates to a clean process for the degradation of steroidal sapogenin to produce 16-dehydropregnenolone and its analogs. The pure or the crude pseudo steroidal sapogenin, derived from steroidal sapogenin, dissolved in organic solvent, reacts with hydrogen peroxide with or without metal compound and acid as catalyst, and the crude products directly go through elimination and hydrolization in the presence of base to give 16-Dehydropregnenolone or its analog, accompanied with the other product 4R(or S)-methyl-5-hydroxy-pentate, which is converted to 4R(or S)-methyl-δ-pentyl lactone after acidification and extraction from the water layer. This technology improved the utilizing degree of steroidal sapogenin, improved the yield, and cleared up the chromium pollution in the former technique. In a word, the method disclosed in this invention is more suitable for manufacture.
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Page/Page column 4
(2008/06/13)
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- A lactosylated steroid contributes in vivo therapeutic benefits in experimental models of mouse lymphoma and human glioblastoma
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Various mono- and disaccharides were grafted onto a steroid backbone. Whereas in vitro these glycosylated steroids had no cytotoxic effects on six different human cancer cell lines, several of the glycosylated steroids under study did significantly modify the levels of in vitro migration of the human U373 glioblastoma, the A549 non-small-cell-lung cancer (NSCLC), and the PC-3 prostate cancer cells, with more pronounced effects in the case of a monosubstituted β-L-fucopyranosyl-steroid (19), a monosubstituted β-D-isomaltosyl-steroid (22), and a monosubstituted β-D-lactosyl- steroid (24). These three compounds significantly increased the survival of conventional mice grafted subcutaneously with the P388 lymphoma, a lymphoma that metastasizes toward the liver. In vivo, the monosubstituted β-D-lactosyl-steroid (24) also increased the antitumor effectiveness of cisplatin, a cytotoxic pro-apoptotic drug, in the case of the P388 lymphoma model. This compound also increased the survival of immunodeficient mice into whose brains human U373 glioblastoma cells had been orthotopically grafted.
- Ingrassia, Laurent,Nshimyumukiza, Prosper,Dewelle, Janique,Lefranc, Florence,Wlodarczak, Lise,Thomas, Stéphanie,Dielie, Gwena?l,Chiron, Christelle,Zedde, Chantal,Tisnès, Pierre,Van Soest, Rob,Braekman, Jean-Claude,Darro, Francis,Kiss, Robert
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p. 1800 - 1807
(2007/10/03)
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- Synthesis of Novel D-Seco-Pregnenes
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A new synthetic route was developed for the preparation of trans-3β-hydroxy-16,17-seco-pregna-5,17(20)-dien-16-al, using Grob fragmentation as the key step. This seco-steroid contains a formyl group and an unsaturated side-chain in a sterically favourable position, and is therefore a promising starting material for the synthesis of novel condensed steroid heterocycles.
- Woelfling, Janos,Magyar, Angela,Schneider, Gyula
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p. 1387 - 1393
(2007/10/03)
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- A facile 1,5-rearrangement of β-formylenamides and cleavage of esters catalysed by Pseudomonas fluorescens
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β-Formylenamides undergo a facile 1,5-rearrangement of their N-acetyl groups under the influence of the soil bacterium Pseudomonas fluorescens to afford β-acetoxyenones in good yields. Further, the soil microorganism efficiently cleaves steroidal and non-steroidal acetates to alcohols.
- Bora,Longchar,Chetia,Kumar,Boruah,Sandhu
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p. 2269 - 2271
(2007/10/03)
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- Synthesis and in vitro activity of some epimeric 20α-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17α-hydroxylase/c17,20-lyase and 5α-reductase
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Some epimeric 20-hydroxy, 20-oxime, 16α, 17α-, 17,20- and 20,21-aziridine derivatives of progesterone were synthesized and evaluated as inhibitors of human 17α-hydroxylase/C17,20-lyase (P450(17α)) and 5α-reductase (5α-R). The reduction of 16-dehydropregenolone acetate (3a) was reinvestigated. NaBH4 in the presence of CeCl3 gave better stereoselectivity for 20β-ol [20α/20β-OH (4α/4β)=1/2.7] than LTBAH or the Meerwein-Pondroff method reported; reduction with Zn in HOAc formed exclusively 20α-ol (4αb). The 20α- and 20β-hydroxy-4,16-pregnadien-3-one (9α) and (9β) were synthesized from the alcohols 4αb and 4βb. Several 20-oxime pregnadienes and 16α,17α-, 17,20- and 20,21-aziridinyl-5-pregnene derivatives were also synthesized. LiAlH4 reduction of the 16-en-20-oxime (12b) yielded 20 (R)-(13a) and 20(S)-17α,20-aziridine (13b) and 20(R)-17β,20-aziridine (14a). Several compounds inhibited the human P450(17α) with greater potency than ketoconzole. The 5α-R enzyme assay showed that while (9α) did not have any activity, (9β) and (3b) were potent 5α-reductase (IC50=21 and 31nM) inhibitors with activities similar to finasteride. The 20-oximes (17a) and (17b) were potent dual inhibitors for both 5α-R (IC50=63 and 115nM, compared to 33nM for finasteride) and P450(17α) (IC50=43 and 25nM, compared to 78nM for ketoconazole). Copyright (C) 1998 Elsevier Science Ltd.
- Ling, Yang-Zhi,Li, Ji-Song,Kato, Katsuya,Liu, Yang,Wang, Xin,Klus, Gregory T.,Marat, Kirk,Nnane, Ivo P.,Brodie, Angela M. H.
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p. 1683 - 1693
(2007/10/03)
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- Synthesis of 16-dehydro-20-oxopregnanes from 17α,20-epoxy-23,24-dinorcholan-22-oic acids. Highly stereospecific oxirane → allyl alcohol isomerization of an epoxycarboxylic acid
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A microbial degradation product of natural sterols was converted into traditional precursor of steroid syntheses by a simple sequence. The title isomerization, the key step, was investigated to demonstrate a concerted mechanism, in which a cyclic transition state, involving the oxirane oxygen, the β- and γ-carbon, the γ-proton to be removed and the catalyst coordinated by the carboxylate group, is postulated.
- Toro, Andras,Pallagi, Istvan,Ambrus, Gabor
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p. 7651 - 7654
(2007/10/02)
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- Transformed steroids 195. Introduction of the 9α-hydroxygroup into Δ5-3β-hydroxysteroids by Circinella sp. mold
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A preparative method of 9α-hydroxylation of Δ5-3β-hydroxysteroids using the fungi of Circinella sp.IOKh-1220 not capable of modifying the ring A has been developed.It is established that the yields of the main and the side products greatly depend on the transformation conditions, mycelium age, and the structure of the steroid substrate.Under the optimal transformation conditions novel 9α-hydroxysubstituted derivatives of androstenolone, pregnenolone, 16-dehydro-16α,17α-epoxy-, and 16α-methoxypregnenolone have been obtained in 36-80percent yields. - Key words: hydroxylation, Δ5-3β-hydroxysteroids, Δ5-3β,9α-dihydroxysteroids, Circinella sp.
- Voishvillo, N. E.,Istomina, Z. I.,Kamernitsky, A. V.
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p. 689 - 695
(2007/10/02)
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- Δ16-20-Ketosteroids by C2-Elongation from Δ16-17-Substituted Steroids
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Reactions of corticoid precursor steroids with a Δ16-double bond and iodine, trimethylsilyl, tributylstannyl or trifluoromethanesulfonyloxy groups in 17-position were studied with the aim of introducing an acyl substituent in 17-position.Starting with the 17-trimethylsilyl compounds, using acyl chlorides and AlCl3 as a catalyst, a mixture of chlorinated compounds were obtained, among others.Better results gave palladium-catalyzed reactions, such as the cross-coupling of 17-tributylstannyl compounds with acyl chlorides or the substitution of the 17-iodides or the 17-triflates by vinyl ethers.In the reaction of the 17-iodides, different protecting groups are tolerated; thus this method is of general use.No Δ16-17-triflates were obtained by the reaction of androsta-4-ene-3,17-dione or androsta-1,4-diene-3,17-dione with trifluoromethanesulfonyl anhydride.This is a limitation of the triflate method, which in the other cases gives the best yields (>80percent).
- Schweder, Bernd,Uhlig, Egon,Doering, Manfred,Kosemund, Dirk
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p. 439 - 444
(2007/10/02)
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- CATALYTIC REARRANGEMENT OF α-D-GLUCOSE 1,2-ORTHOACETATE DERIVATIVES OF PREGNENOLONE AND 16-DEHYDROPREGNENOLONE
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The rearrangement of pregnenolone and 16-dehydropregnenolone α-D-glucose orthoacetates in the presence of mercuric bromide is, because of the high specific selectivity and satisfactory yields of the desired β-D-glucosides, the most effective method of glycosylating the steroids mentioned.
- Samoshina, N. F.,Denisenko, V. A.,Novikov, V. L.,Uvarova, N. I.
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p. 177 - 182
(2007/10/02)
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- A Ready Conversion of a Pregnane-20-carboxaldehyde to 17α-Hydroxypregnan-20-ones and Pregn-16-en-20-ones
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Reaction of (20S)-5α-chloro-3β-hydroxypregnane-20-carboxaldehyde (9, prepared in two steps from stigmasterol) with oxygen and potassium tert-butoxide, followed by trimethyl phosphite treatment, afforded 5α-chloro-3β,17α-dihydroxypregnan-20-one (6) and 3β,17α-dihydroxypregn-5-en-20-one (7).This mixture was converted into 7 by potassium hydroxide treatment, and into 17α-hydroxypregn-4-ene-3,20-dione (8) by reaction with pyridinium dichromate followed by potassium hydroxide treatment.Bromination-dehydrobromination of 9, in one or two steps, afforded (Z)- and (E)-5α-chloro-3β-hydroxypregn-17(20)-ene-20-carboxaldehyde (11).Reaction of 11 with oxygen and potassium hydroxide gave 5α-chloro-3β-hydroxypregn-16-en-20-one (12), which was converted to 3β-hydroxypregna-15,6-dien-20-one (13) by further potassium hydroxide treatment, and to pregna-4,16-diene-3,20-dione (14) by Oppenauer reaction using excess aluminium isopropoxide.
- Biancini, Bruno,Caciagli, Valerio,Centini, Felice,Eletti-Bianchi, Giancarlo,Re, Luciano
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p. 1829 - 1835
(2007/10/02)
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