- Reactivity of Steroidal 1-Azadienes toward Carbonyl Compounds under Enamine Catalysis: Chiral Penta- and Hexacyclic Steroids
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The synthesis and reactivity of a steroidal N-sulfonyl-1-azadiene, derived from 16-dehydropregnenolone acetate, toward carbonyl compounds under enamine catalysis is disclosed. An unexpected annulation reaction was observed involving an initial stereoselec
- Lopes, Susana M. M.,Gomes, Clara S. B.,Pinho Melo, Teresa M.V.D.E.
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- Analysis of C-H...O intermolecular interactions in 4-androstene-3,17-dione
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4-Androstene-3,17-dione was synthesized for its crystallographic analysis and to investigate the role of intra- and intermolecular interactions in steroids. It crystallizes in the orthorhombic space group P212 121 with unit cell parameters, a = 7.330(2) A, b = 13.095(11) A, c = 16.856(17) A, V = 1,618(5) A3 and Z = 4. The structure has been solved by direct methods using X-ray diffraction techniques and the refined final reliability index for the computed structure is 0.033 for 1,655 observed reflections. Two six-membered rings B and C exist in chair conformation while ring A occupies a sofa conformation. The five-membered ring D depicts envelope conformation. The C-H...O intermolecular hydrogen interaction results into a ring like configuration which makes the dimers.
- Rajnikant, Verma,Dinesh, Dinesh,Aziz, Nusrat,Gupta
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- Synthesis of 7α-hydroxy-dehydroepiandrosterone and 7β-hydroxy-dehydroepiandrosterone
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The fermentation of dehydroepiandrosterone synthesized from the starting material diosgenin using Mucor racemosus produced 7α-hydroxy- dehydroepiandrosterone and 7β-hydroxy-dehydroepiandrosterone. The bioactivity of the microbial metabolites is also discussed. The species M. racemosus was isolated by screening among stains from soil samples collected from various parts of China.
- Li, Heping,Liu, Hong-Min,Ge, Wenzhong,Huang, Lihua,Shan, Lihong
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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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- D-Ring modification of steroids: synthesis of isoxazole annulated steroids from des D-formyl alkyne via 1,3-dipolar cycloaddition reaction
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The reaction of 17,17-dichloro-androst-16(E)-chloromethylene with secondary amine base afforded substitution products of exocyclic D-ring ketones, in contrast to the reaction of alkaline base which cleaved steroidal D-ring to des-D formyl alkyne. The des-
- Nongthombam, Geetmani Singh,Boruah, Romesh Chandra
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p. 2853 - 2861
(2021/08/06)
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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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- Synthesis of D-Ring Annulated Pyridosteroids from β-Formyl Enamides and Their Biological Evaluations
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Herein, we report the synthesis of a novel class of substituted androst[17,16-b]pyridines (pyridosteroids) from the reaction of β-formyl enamides with alkynes in high yields. The optimized reaction protocol was extended to acyclic and cyclic β-formyl enamides to afford nonsteroidal pyridines. Cell survival assay of all compounds were carried against prostate cancer PC-3 cells wherein 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine showed the highest cytotoxic activity. Phase contrast microscopy and flow cytometry studies exhibited marked morphological features characteristic of apoptosis in 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine and abiraterone treated PC-3 cells. The treatment of 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine induces G2/M phase cell cycle arrest in prostate cancer PC-3 cells. Enhancement of apoptotic inductions of PC-3 cells by 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine and abiraterone through the activation of caspases-6, -7, and -8 pathways were supported by qRT-PCR. In silico study of the compound 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine showed stable and promising interaction with the key caspase proteins. Our studies revealed that the pyridosteroid 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine, bearing pyridine-2,3-dicarbethoxy pharmacophore, facilitated initiation of caspase-8 and activates downstream effectors caspase-6 and caspase-7 and thereby triggering apoptosis of PC-3 cancer cells.
- Nongthombam, Geetmani Singh,Borah, Kasmika,Muinao, Thingreila,Silla, Yumnam,Pal, Mintu,Deka Boruah, Hari Prasanna,Boruah, Romesh Chandra
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supporting information
p. 11 - 27
(2019/01/11)
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- METHODS FOR PREPARATION OF BILE ACIDS AND DERIVATIVES THEREOF
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The present application relates to a method of preparing compounds of Formula (I) or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof, R1 is H, α-OH, β-ΟΗ, or an oxo group.
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- PREGNANE-OXIMINO-AMINOALKYLETHERS AND PROCESS FOR PREPARATION THEREOF, USEFUL AS ANTIDIABETIC AND ANTIDYSLIPIDEMIC AGENTS
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The present invention relates to the synthesis of pregnane-oximino-aminoalkyl-ethers and their antidiabetic and antidyslipidemic activities. More particularly, the invention relates to the synthesis of compounds of formula 3 and biological profile thereof. Further the invention relates to compounds of formula 3 and pharmaceutically acceptable salts thereof.
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(2014/08/07)
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- 17-Oximino-5-androsten-3β-yl esters: Synthesis, antiproliferative activity, acute toxicity, and effect on serum androgen level
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The 17-oximino-5-androsten-3β-yl esters (10a- 10j) were synthesized from commercially available (25R)- 5-Spirosten-3β-ol (Diosgenin) (4) as starting material. The synthesized compounds were evaluated for their antiproliferative activity against prostate specific cancer cell line DU-145, acute toxicity, and effect on serum androgen level and were compared with Finasteride used as positive control. Some of the compounds exhibited better cytotoxicity and antiandrogenic activity than the reference control. The detailed synthesis, spectroscopic data, and biological evaluation for the synthesized compounds are reported. Springer Science+Business Media, LLC 2010.
- Dhingra, Neelima,Bhardwaj, Tilak Raj,Mehta, Neeraj,Mukhopadhyay, Tapas,Kumar, Ashok,Kumar, Manoj
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p. 817 - 825
(2012/05/04)
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- Expedient synthesis of some novel pregnane derivatives and their evaluation as anti-oxidant and anti-dyslipidemic agents
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Synthesis of a number of novel pregnane derivatives has been described in detail. They were prepared by reaction of 3β-hydroxy-5, 16-pregnadiene-20-one (2) with diethylene glycol, 2-methoxy ethanol, 1,2-propane diol, p-chloroaniline and p-fluoroaniline, respectively. The structures of these newly synthesized compounds have been established on basis of physical, analytical and spectral data. These pregnane derivatives have been evaluated for their anti-dyslipidemic activity (Triton model) and in vitro antioxidant activities. Out of the 12 compounds tested, 3 of them showed potent anti-dyslipidemic activity and 7 showed potent antioxidant and scavenger of oxygen free radicals. Springer Science+Business Media, LLC 2010.
- Sethi, Arun,Bhatia, Gitika,Khanna, Ashok K.,Khan, Mohammad Mobin,Bishnoi, Abha,Pandey, Anil K.,Maurya, Atul
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body text
p. 36 - 46
(2012/03/10)
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- Synthesis, antiproliferative activity, acute toxicity and assessment of the antiandrogenic activities of new androstane derivatives
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A number of 17-oxo-5-androsten-3β-yl esters (9a-9f) and 3β-alkoxy-5-androsten-17-ones (11a-11e) were synthesized from commercially available (25R)-5-spirosten-3β-ol (Diosgenin) (4) as starting material. The synthesized compounds were evaluated for their antiproliferative activity against the prostate-specific cancer cell line DU-145, acute toxicity and effect on serum androgen levels, and compared with finasteride as positive control. Some of the compounds exhibited better cytotoxicity and antiandrogenic activity than the reference control. The detailed synthesis, spectroscopic data and biological activity of the synthesized compounds are reported.
- Dhingra, Neelima,Bhardwaj,Mehta, Neeraj,Mukhopadhyay, Tapas,Kumar, Ashok,Kumar, Manoj
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scheme or table
p. 1055 - 1063
(2012/07/28)
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- Synthesis, antiproliferative, acute toxicity and assessment of antiandrogenic activities of some newly synthesized steroidal lactams
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The 17-oxo-17a-aza-d-homo-5-androsten-3β-yl esters (13-22) were synthesized from commercially available (25R)-5-spirosten-3β-ol (Diosgenin) (6) as starting material. The synthesized compounds were evaluated for their antiproliferative activity, acute toxicity and effect on serum androgen level and were compared with Finasteride as positive controls. Some of the compounds exhibited better cytotoxicity and antiandrogenic activity than the reference control. The detailed synthesis, spectroscopic data and pharmacological screening for the synthesized compounds were reported.
- Dhingra, Neelima,Bhardwaj,Mehta, Neeraj,Mukhopadhyay, Tapas,Kumar, Ashok,Kumar, Manoj
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scheme or table
p. 2229 - 2236
(2010/06/16)
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- A SIMULTANEOUS METHOD FOR THE PREPARATION OF A MIXTURE OF 3- ACETOXY-17-ACETAMIDO-16-FORMYL-ANDROST-5,17-DIENE AND 3- ACETOXY-2'-CHLORO-5-ANDROSTENO[17,16-B]PYRIDINE
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The present invention relates to preparation and biological evaluation of 3-acetoxy-17- acetamido-16-formyl-androst-5,17-diene (4) and 3-acetoxy2''-chloro-5-androsteno [17,16- b]pyridine (5) as gastric proton pump inhibitor and their comparison to that of omeprazole, a clinically employed anti-gastric ulcer drug. Compound (4) exhibited dose dependent inhibition of histamine-stimulated acid secretion in gastric parietal cell with an IC50 value comparable to cimetidine. No mortality or behavioral abnormality of Swiss albino mice was observed under single-dose level of 1g/Kg body weight of compound (4). Compound (4) further exhibited excellent anti ulcer activity in vivo against indomethacin induced ulcer.
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(2009/10/30)
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- Convenient synthesis of new pregnenolone oximinyl oxalate dimers
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Three new symmetrical pregnenolone oxyminyl oxalate dimers (8-10) were synthesized from the corresponding pregnenolone oximes (3, 5, and 7) at room temperature. All dimers were characterised by spectroscopic means, notably HRFABMS and comprehensive NMR spectroscopic data analyses.
- Nahar,Sarker,Turner
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experimental part
p. 315 - 318
(2009/04/03)
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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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- Synthesis of new chiral 2,2′-bipyridine ligands and their application in Copper-catalyzed asymmetric allylic oxidation and cyclopropanation
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A series of modular bipyridine-type ligands 1 and 3-9 has been synthesized via a de novo construction of the pyridine nucleus. The chiral moieties of these ligands originate from the isoprenoid chiral pool, namely, β-pinene (10 → 1), 3-carene (14 → 3 and 5), 2-carene (28 → 4), α-pinene (43 → 6-8), and dehydropregnenolone acetate (48 → 9), respectively. Copper(I) complexes, derived from these ligands and (TfO)2Cu (1 mol%) upon an in situ reduction with phenylhydrazine, exhibit good enantioselectivity (up to 82% ee) and unusually high reaction rate (typicaly 30 min at room temperature) in allylic oxidation of cyclic olefins (52 → 53). Copper-catalyzed cyclopropanation proceeded with ≤76% enantioselectivity and ~3:1 to 99:1 trans/cis-diastereoselectivity (54 → 55 + 56). The level of the asymmetric induction is discussed in terms of the ligand architecture that controls the stereochemical environment of the coordinated metal.
- Malkov, Andrei V.,Pernazza, Daniele,Bell, Mark,Bella, Marco,Massa, Antonio,Teply, Filip,Meghani, Premji,Kocovsky, Pavel
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p. 4727 - 4742
(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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