- Crystal structure of 3β-acetoxy-pregna-5,16-dien-20-one (16 DPA)
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The title compound, 3β-acetoxy-pregna-5,16-dien-20-one, C 23H32O3, has been synthesized by acetylation followed by oxidation of diosgenin and its crystal structure has been solved from single crystal X-ray diffraction data. The compound crystallizes into orthorhombic space group P212121 with unit cell parameters: a = 6.031(4) A, b = 12.481(2) A, c = 27.162(5) A, Z = 4. The crystal structure has been refined to R = 0.0597 for 1291 observed reflections. Rings A and C of the compound are in chair conformation whereas ring B is in half-chair conformation. Ring D is in envelop conformation. The A/B ring junction is quasi-trans, while ring systems B/C and C/D are trans fused about the C8-C9 and C13-C14 bonds, respectively. The steroid nucleus has a small twist, as shown by the C19-C10...C13-C18 pseudo-torsion angle of 9.5°. The crystal packing is determined by a pair of weak C-H...O hydrogen bonds in addition to van der Waals interactions.
- Bandhoria, Pankaj,Gupta, Vivek K.,Gupta,Jain,Varghese
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- Synthesis of silyl enol and silyl dienol ethers of 20-Oxosteroids: The effect of β-substituents
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An efficient method to obtain regioselectively the title compounds is described. Experimental studies concerning the effect of β-substituents on the generation of β-substituted silyl enol ethers made feasible for the first time the isolation and identification of the products resulting from the unstable thermodynamic silyl enol ether.
- Moreno, Maria Jose S. M.,Martins, Rosa Maria L. M.,Sa E Melo, Maria Luisa,Campos Neves, Andre S.
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Read Online
- Facile green synthesis of 16-dehydropregnenolone acetate (16-DPA) from diosgenin
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Chromium- and MnO2-free green synthesis of industrially important steroidal drug intermediate 16-dehydropregnenolone acetate (16-DPA) starting from diosgenin is reported. The reaction sequence involves three steps: acetolysis followed by acetylation, oxidation, and hydrolysis. In the first step, Ac2O was used both as reagent and solvent in combination with a Lewis acid (AlCl3), which led to considerable reduction of high temperature and pressure requirements of earlier processes. The oxidation step was made catalytic with the use of KMnO4(5 mol%) in the presence of co-oxidant NaIO4, leading to less waste generation (of chromium, MnO2, etc.). Minimization of the temperature, pressure, time consumption, and use of nontoxic solvents makes the process very handy and simple.
- Baruah, Diganta,Das, Ram Nath,Konwar, Dilip
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Read Online
- A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors
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4-Androstenedione (4-AD) and progesterone (PG) are two of the most important precursors for synthesis of steroid drugs, however their current manufacturing processes suffer from low efficiency and severe environmental issues. In this study, we decipher a dual-role reductase (mnOpccR) in the phytosterols catabolism, which engages in two different metabolic branches to produce the key intermediate 20-hydroxymethyl pregn-4-ene-3-one (4-HBC) through a 4-e reduction of 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) and 2-e reduction of 3-oxo-4-pregnene-20-carboxyl aldehyde (3-OPA), respectively. Inactivation or overexpression of mnOpccR in the Mycobacterium neoaurum can achieve exclusive production of either 4-AD or 4-HBC from phytosterols. By utilizing a two-step synthesis, 4-HBC can be efficiently converted into PG in a scalable manner (100 gram scale). This study deciphers a pivotal biosynthetic mechanism of phytosterol catabolism and provides very efficient production routes of 4-AD and PG.
- Peng, Haidong,Wang, Yaya,Jiang, Kai,Chen, Xinru,Zhang, Wenlu,Zhang, Yanan,Deng, Zixin,Qu, Xudong
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supporting information
p. 5414 - 5420
(2021/02/05)
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- Continuous Flow Synthesis of 16-Dehydropregnenolone Acetate, a Key Synthon for Natural Steroids and Drugs
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A telescoped multistep process to provide the continuous delivery of 16-dehydropregnenolone acetate (16-DPA) from diosgenin is described. The method was evaluated through batch screenings that helped to identify critical bottlenecks and flowability, and the best conditions were optimized in flow systems before the individual steps were telescoped together into a single integrated flow process. Further highlights of our approach include the use of efficient in-line extraction operations and reaction monitoring, the avoidance of time-consuming purifications between steps, and improvement of efficiency and safety standards.
- Mancino, Valentina,Cerra, Bruno,Piccinno, Alessandro,Gioiello, Antimo
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supporting information
p. 600 - 607
(2018/05/14)
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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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Page/Page column 56
(2017/02/24)
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- Some observations on solasodine reactivity
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This article presents new transformations of solasodine – a representative steroid alkaloid sapogenin from the Solanum family. Oxidation of N,O-diacetylated solasodine with either NaNO2/BF3·Et2O or t-BuONO/BF3·Et2O resulted in partial degradation of the side chain to (20S)-3β-acetoxypregn-5-ene-20,16β-carbolactone (vespertilin acetate). The same starting compound when treated with TMSOTf afforded the corresponding pseudosapogenin after aqueous work-up. However, when the crude reaction mixture was directly subjected to purification on a silica gel column, efficient autoxidation to pregna-5,16-dien-3β-ol-20-one acetate was observed. One-step synthesis of this important drug intermediate from spirosolan alkaloids may be potentially exploited for large-scale production of steroid hormones.
- Jastrzebska, Izabella,Morzycki, Jacek W.
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- 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 of steroidal derivatives containing substituted, fused and spiro pyrazolines
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An efficient and facile synthesis of fused, substituted and spiro pyrazoline steroid derivatives through a cycloaddition reaction of different α,β-unsaturated ketones with hydrazine acetate in acetic acid is reported. Depending on the starting material, the ring closure reaction provided a mixture of two steroidal pyrazoline epimers that were separated and studied by NMR techniques. In one case it was possible to isolate and characterize the hydrazone derivative as the reaction intermediate, which confirms the mechanism proposed in the literature [11,25,26].2014 Published by Elsevier Inc.
- Romero-López, Anabel,Montiel-Smith, Sara,Meza-Reyes, Socorro,Merino-Montiel, Penélope,Vega-Baez, José Luis
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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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p. 3887 - 3893
(2013/10/22)
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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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- 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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scheme or table
p. 817 - 825
(2012/05/04)
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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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- 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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- A PROCESS FOR THE PREPARATION OF 16-DEHYDROPREGENOLONE ACETATE ( 16-DPA)
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The present invention provides an improved process for the preparation of 16-dehydropregenolone acetate [16-DPA], wherein pseudodiosgenin diacetate (PDA) is oxidized to diosone by catalytic amount of KMnO4 in the presence of a co oxidant selected from NalO4, NaClO3, NaClO4 and NalO3. In the present invention MnO2 produced by KMnO4 during the oxidation process is reoxidized by the use of cooxidant, which makes the whole process for the production of 16-DPA more economically viable, simple, and environmentally benign.
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(2008/06/13)
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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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p. 970 - 973
(2007/10/03)
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- A new protocol for synthesis of α,β-unsaturated ketones using zirconium tetrachloride under microwave irradiation
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A facile one-pot synthesis of α,β-unsaturated carbonyl compound has been accomplished from ZrCl4 mediated condensation of α-bromo ketones with aryl aldehydes under microwave irradiation.
- Bora, Utpal,Saikia, Anil,Boruah, Romesh C.
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p. 2523 - 2526
(2007/10/03)
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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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p. 271 - 277
(2007/10/03)
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- Chloro- or bromo-trimethylsilane induced rapid and quantitative acid-ester conversion for steroid based alcohols with various carboxylic acids under solvent free conditions
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Steroid based higher alcohols are rapidly esterified in quantitative yield with a number of carboxylic acids in the presence of TMSCl or TMSBr generally under solvent free conditions.
- Goswami, Papori,Hazarika, Saroj,Borah, Parinita,Chowdhury, Pritish
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p. 678 - 682
(2007/10/03)
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- A one-pot efficient process for 16-dehydropregnenolone acetate
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A one-pot eco-friendly and efficient transformation of steroidal sapogenin diosgenin (1) and solasodine (2) to a commercially very important drug intermediate 16-dehydropregnenolone acetate (16-DPA, 9) was developed with an overall yield of 75%. This process can easily be exploited for industrial production.
- Goswami, Amrit,Kotoky, Rumi,Rastogi, Romesh C.,Ghosh, Anil C.
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p. 306 - 308
(2013/09/06)
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- Further syntheses of cyproterone acetate
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The present invention relates to improved methods for synthesising cyproterone acetate (17α-Acetoxy-6-chloro-1α, 2α-methylene-4,6-pregnadiene-3,20-dione) from solasodine. The methods of the invention are shorter as those of the prior art and therefore more economic.
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Page/Page column 12
(2010/02/07)
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- Ceric ammonium nitrate (CAN) - A useful catalyst for the rapid and high-yield esterification of carboxylic acids and alcohols with special reference to steroid and other multi-functional natural products
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Ceric ammonium nitrate (CAN) acts as a versatile catalyst for the esterification of carboxylic acids and alcohols, including steroids and other multi-functional natural products, in excellent yields under mild and convenient reaction conditions.
- Goswami,Chowdhury
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p. 955 - 957
(2007/10/03)
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- Synthesis and evaluation of novel steroidal oxime inhibitors of P450 17 (17α-hydroxylase/c17-20-lyase) and 5α-reductase types 1 and 2
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17α-Hydroxylase/C17-20-lyase (P450 17, CYP 17) and 5α-reductase are the key enzymes in androgen biosynthesis and targets for the treatment of prostate cancer and benign prostatic hyperplasia. In the search of inhibitors for both enzymes, 23 pregnenolone- or progesterone-based steroids were synthesized bearing an oxime group connected directly or via a spacer to the steroidal D-ring. Tested for inhibition of human and rat P450 17, some pregnenolone (9, 11, 14) and a series of progesterone compounds (17-20) turned out to be highly active inhibitors of the human enzyme. The most active compound was Z-21-hydroxyiminopregna-5,17(20)-dien-3β-ol (9) showing K(i) values of 44 and 3.4 nM for the human and rat enzymes, respectively, and a type II UV-difference spectrum indicating a coordinate bond between the oxime group and the heme iron. In contrast to the pregnenolones which showed no inhibition of 5α-reductase isozymes 1 and 2, the progesterones 16, 17, 20, 21, and 23 showed marked inhibition, especially toward the type 2 enzyme. Compounds 17 and 20 were identified as potent dual inhibitors of both P450 17 and 5α-reductase. Tested for selectivity, the most potent P450 17 inhibitors 9, 10, and 14 showed no or only marginal inhibition of P450 arom, P450 scc, and P450 TxA2. Selected compounds were tested for inhibition of the target enzymes using whole-cell assays. Compounds 9-11 strongly inhibited P450 17 being coexpressed with NADPH-P450 reductase in E. coli cells, and 16, 20, and 23 markedly inhibited 5α-reductase expressed in HEK 293 cells. Tested for in vivo activity, 9 (0.019 mmol/kg) decreased the plasma testosterone concentration in rats after 2 and 6 h by 57% and 44%.
- Hartmann,Hector,Haidar,Ehmer,Reichert,Jose
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p. 4266 - 4277
(2007/10/03)
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- Deoximation using Dess-Martin Periodinane: Regeneration of ketones from ketoximes
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The Dess-Martin Periodinane (DMP), [1,1,1-triacetoxy-1,1-dihydro-1,2- benziodoxol-3(1H)-one], regenerates ketones from the corresponding ketoximes rapidly at room temperature in very high yields.
- Chaudhari, Sachin S.,Akamanchi, Krishnacharya G.
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p. 3209 - 3212
(2007/10/03)
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- Degradation of Solasodine to 16β,22-Epoxy-23,24-dinorchol-5-ene-3β,22β-diol and Partial Synthesis of (23S)-23-Hydroxysolasodine
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(22R,23S,25R)-N-Chloro-22,26-epiminocholest-5-ene-3β,16β,23-triol (11) and its 3,16,23-O-triacetyl derivative 15 were prepared from solasodine (1).Treatment of 11 or 15 with sodium methanolate yielded the 22,23-secoaldehyde 16 as major product (Grob fragmentation) and (23S)-23-hydroxysolasodine (2) as minor product (Ruschig reaction).Hydrolysis of 16 with methanolic hydrochloric acid afforded 16β,22-epoxy-23,24-dinorchol-5-ene-3β,22β-diol (17) and its 22-O-methyl derivative 18, the 3-O-acetate 19 of which was oxidzed to the known acetyldiosgenin lactone (20), thus confirming the structures of 16-19.Compound 2 was shown to be identical in every respect with a rare spirosolane alkaloid, recently isolated from some Solanum species.Photolysis of (22R,23S,25R)-3β,16β-diacetoxy-N-chloro-22,26-epiminocholest-5-en-23-ol (10) yielded also via 22,23-carbon-carbon cleavage (20S)-3β,16β-diacetoxypregn-5-ene-20-carbaldehyde (21) as major product, which was converted by treatment with methanolic hydrochloric acid into the compound 18. Key Words: Solasodines/Chol-5-ene-3β,22β-diol, 16β,22-epoxy-23,24-dinor-/Solanum steroid alkaloids/Steroids/Alkaloids/Ruschig reaction/Grob fragmentation.
- Quyen, Le thi,Ripperger, Helmut,Adam, Guenter,Schreiber, Klaus
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p. 167 - 172
(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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- A FACILE PROCEDURE FOR SELECTIVE CONVERSION OF KETALS TO CARBONYL COMPOUNDS
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Ketals are selectively cleaved by aluminium triiodide (AlI3) to the corresponding carbonyl compounds in excellent yields.However, thioketals are not affected by this reagent.
- Barua, Nabin C.,Sarmah, Parijat
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p. 4703 - 4704
(2007/10/02)
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- A Further Synthesis of the Corticosteroid Side Chain starting with a Suitable 17-Ketone
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The readily available olefin (8) is easily converted into the synthetically useful enamide (15) via the nitrosyl chloride adduct (9).
- Barton, Derek H. R.,Zard, Samir Z.
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p. 2191 - 2192
(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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- Steroid saponins
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Novel steroid saponin compounds (XR-1) and (XR-2) are extracted from Solanam aculeatissimum, a plant belonging to the Solanum genus, and 16-dehydropregnenolone is obtained by hydrolyzing the said compounds, subjecting the hydrolyzed product to Marker's degradation, and treating the obtained product with aqueous alkali.
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- Process for preparing Δ9(11) and/or Δ16 -unsaturated sternoids
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A process for preparing a Δ9(11) - and/or Δ16 -unsaturated steroid comprises heating the corresponding steroid of the pregnane series substituted by 9α-chloro- and/or 16α-chloro- or 17α-acyloxy, in an inert, aprotic high-boiling solvent at 180°-350° C.
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