- Synthesis and structure determination of 3β-hydroxyandrost-5-en-17-one (C19H28O2·CH3OH)
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3β-Hydroxyandrost-5-en-17-one (C19H28O 2.CH3OH) has been prepared for undertaking its crystallographic analysis and to investigate the role of intra- and intermolecular interactions in steroids. The title compound crystallizes in the orthorhombic space group C2221 with unit cell parameters a = 6.7892(17), b = 12.624(2), and c = 41.136(5) A; V = 3525.7(12) A3 and Z = 8. The three-dimensional structure has been solved by direct methods. The final reliability index for the computed structure is 0.050 for 1088 observed reflections. Ring A exist in chair conformation, Ring B in half-chair conformation, and the Ring C assumes a distorted chair conformation. The five-membered Ring D adopts half-chair conformation. The A/B ring junction is quasi-trans while as B/C and C/D are trans-fused. The oxygen atom of the solvent molecule (CH3OH) is involved in O-H···O intermolecular interaction.
- Verma, Rajnikant,Jasrotia, Dinesh,Sawhney, Anshu,Bhat, Mousmi,Gupta
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Read Online
- A steroidogenic pathway for sulfonated steroids: The metabolism of pregnenolone sulfate
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In many tissues sulfonated steroids exceed the concentration of free steroids and recently they were also shown to fulfill important physiological functions. While it was previously demonstrated that cholesterol sulfate (CS) is converted by CYP11A1 to pregnenolone sulfate (PregS), further conversion of PregS has not been studied in detail. To investigate whether a steroidogenic pathway for sulfonated steroids exists similar to the one described for free steroids, we examined the interaction of PregS with CYP17A1 in a reconstituted in-vitro system. Difference spectroscopy revealed a Kd-value of 74.8 ± 4.2 μM for the CYP17A1-PregS complex, which is 2.5-fold higher compared to the CYP17A1-pregnenolone (Preg) complex. Mass spectrometry experiments proved for the first time that PregS is hydroxylated by CYP17A1 at position C17, identically to pregnenolone. A higher Km- and a lower kcat-value for CYP17A1 using PregS compared with Preg were observed, indicating a 40% reduced catalytic efficiency when using the sulfonated steroid. Furthermore, we analyzed whether the presence of cytochrome b5(b5) has an influence on the CYP17A1 dependent conversion of PregS, as was demonstrated for Preg. Interestingly, with 17OH-PregS no scission of the 17,20-carbon-carbon bond occurs, when b5is added to the reconstituted in-vitro system, while b5promotes the formation of DHEA from 17OH-Preg. When using human SOAT-HEK293 cells expressing CYP17A1 and CPR, we could confirm that PregS is metabolized to 17OH-PregS, strengthening the potential physiological meaning of a pathway for sulfonated steroids.
- Neunzig,Sánchez-Guijo,Mosa,Hartmann,Geyer,Wudy,Bernhardt
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Read Online
- Etherification of Hydroxystereoids via Triflates
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Triflates of saturated alcohols are useful in the alkylation of 3- and 17-hydroxysteroids in the presence of hindered amines.The etherification is successful even in those cases where other alkylating agents are noneffective.
- Belostotskii, Anatoly M.,Hassner, Alfred
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Read Online
- Modified bile acids and androstanes—Novel promising inhibitors of human cytochrome P450 17A1
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Cytochromes P450 are key enzymes for steroid hormone biosynthesis in human body. They are considered as targets for the screening of novel high efficient drugs. The results of screening of bile acids and androstane derivatives toward human recombinant steroid 17α-hydroxylase/17,20-lyase (CYP17A1) are presented in this paper. A group of steroids, binding with micromolar or submicromolar affinity (in a range from 9 μM – less than 0.1 μM), was identified. Results presented here showed that these steroidal compounds are able to decrease rate of hydroxylation of essential CYP17A1 substrate – progesterone, while some compounds completely inhibited enzyme activity. Structure-activity relationship (SAR) analysis based on in vitro and in silico studies showed that high affinity of the enzyme to bile acids derivatives is correlated with side chain hydrophobicity and presence of hydroxyl or keto group at C3 position. From the other side, bile acid-derived compounds with more polar side chain or substituents at C7 and C12 positions possess higher Kd values. Among androstane-derived steroids couple of Δ5-steroids with hydroxyl group at C3 position, as well as 16,17-secosteroids, were found to be high affinity ligands of this enzyme. The data obtained could be useful for the design of novel highly efficient inhibitors of CYP17A1, since the bile acids-derived compounds are for first time recognized as effective CYP17A1 inhibitors.
- Dzichenka, Yaraslau,Shapira, Michail,Yantsevich, Aliaksei,Cherkesova, Tatsiana,Grbovi?, Ljubica,Savi?, Marina,Usanov, Sergey,Jovanovi?-?anta, Suzana
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- Deconstructive Oxygenation of Unstrained Cycloalkanamines
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A deconstructive oxygenation of unstrained primary cycloalkanamines has been developed for the first time using an auto-oxidative aromatization promoted C(sp3)?C(sp3) bond cleavage strategy. This metal-free method involves the substitution reaction of cycloalkanamines with hydrazonyl chlorides and subsequent auto-oxidative annulation to in situ generate pre-aromatics, followed by N-radical-promoted ring-opening and further oxygenation by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and m-cholorperoxybenzoic acid (mCPBA). Consequently, a series of 1,2,4-triazole-containing acyclic carbonyl compounds were efficiently produced. This protocol features a one-pot operation, mild reaction conditions, high regioselectivity and ring-opening efficiency, broad substrate scope, and is compatible with alkaloids, osamines, and peptides, as well as steroids.
- Han, Bing,He, Yi-Heng,Pan, Jia-Hao,Wang, Yuan-Rui,Yu, Wei,Zhang, Jian-Wu
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supporting information
p. 3900 - 3904
(2020/02/11)
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- Method for preparing 4-androstenedione from dehydroepiandrosterone acetate
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The invention provides a method for preparing 4-androstenedione from dehydroepiandrosterone acetate. The method comprises the following steps: carrying out a hydrolysis reaction on dehydroepiandrosterone acetate to obtain dehydroepiandrosterone, carrying out an oxidation reaction on the dehydroepiandrosterone to obtain crude 4-androstenedione, adding methanol and dichloroethane to the crude 4-androstenedione, and performing purification to obtain refined 4-androstenedione, wherein the obtained refined 4-androstenedione can be further reacted with potassium tert-butoxide to obtain 5-androstenedione. The method for preparing 4-androstenedione from dehydroepiandrosterone acetate has the following advantages: the preparation process is simple and feasible, and the production rate is improved,so the production values of enterprises are improved; and the cheap dehydroepiandrosterone acetate is used as the raw material to prepare the 4-androstenedione greatly demanded on the market, and the4-androstenedione is reacted to further prepare the 5-androstenedione, so the production cost of the enterprise is saved.
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Paragraph 0026; 0027; 0028; 0032-0034; 0038-0040
(2019/07/04)
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- Comprehensive kinetic and substrate specificity analysis of an arylsulfatase from Helix pomatia using mass spectrometry
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Sulfatases hydrolyze sulfated metabolites to their corresponding alcohols and are present in all domains of life. These enzymes have found major application in metabolic investigation of drugs, doping control analysis and recently in metabolomics. Interest in sulfatases has increased due to a link between metabolic processes involving sulfated metabolites and pathophysiological conditions in humans. Herein, we present the first comprehensive substrate specificity and kinetic analysis of the most commonly used arylsulfatase extracted from the snail Helix pomatia. In the past, this enzyme has been used in the form of a crude mixture of enzymes, however, recently we have purified this sulfatase for a new application in metabolomics-driven discovery of sulfated metabolites. To evaluate the substrate specificity of this promiscuous sulfatase, we have synthesized a series of new sulfated metabolites of diverse structure and employed a mass spectrometric assay for kinetic substrate hydrolysis evaluation. Our analysis of the purified enzyme revealed that the sulfatase has a strong preference for metabolites with a bi- or tricyclic aromatic scaffold and to a lesser extent for monocyclic aromatic phenols. This metabolite library and mass spectrometric method can be applied for the characterization of other sulfatases from humans and gut microbiota to investigate their involvement in disease development.
- Correia, Mário S.P.,Ballet, Caroline,Meistermann, Hannes,Conway, Louis P.,Globisch, Daniel
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p. 955 - 962
(2019/02/09)
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- Synthesis of 3β-methyl ether of dehydroepiandrosterone by biotransformation of 3β-methyl ether of cholesterol with cells of mycobacteria Mycobacterium sp.
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3p-Methyl ether of dehydroepiandrosterone was obtained by microbiological transformation of 3?-methyl ether of cholesterol with Mycobacterium sp. Androstane-3,17-dione, androst-4-ene-3,17-dione, and androsta-1,4-diene-3,17-dione were minor transformation products.
- Andryushina,Stytsenko,Karpova,Yaderets,Zavarzin,Kurilov
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p. 2355 - 2358
(2020/02/18)
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- Steroid compound 3-site hydroxyl configuration inversion method
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The invention discloses a steroid compound 3-site hydroxyl configuration inversion method. The method specifically comprises the following steps that (1) a steroid compound containing a 3-site hydroxyl reacts with an acyl chloride compound; (2) the product obtained in the step (1) and a substituting agent are subjected to SN2 nucleophilic substitution reaction under existing of a phase transfer catalyst; and (3) the product obtained in the step (2) is subjected to a hydrolysis reaction. Compared with a Mitsunobu method, the method does not need to use triphenylphosphine and azodiformate pricedhigher, and accordingly the production cost is greatly lowered; meanwhile, a p-nitrobenzoic acid derivative which seriously affects the water environment does not need to be used, and therefore the method is more environmentally friendly. The method adopts cesium acetate/18-crown ether-6 system to conduct 3-site hydroxyl configuration inversion, can remarkably reduce occurrence of side reactions,accordingly a higher reaction yield is obtained, and the method is finally applicable to industrialized production.
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Paragraph 0051; 0056; 0057
(2018/12/14)
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- STEROIDAL COMPOUND, COMPOSITION CONTAINING THE SAME AND USE THEREOF
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Provided in the present invention are a steroidal compound, a composition containing the same and a use thereof. Specifically, disclosed in the present invention are a steroidal compound as shown in formula (I) and a drug composition containing the same, or a crystal form, a pharmaceutically acceptable salt, a hydrate or solvate, a stereoisomer, a prodrug, a metabolite or an isotopic variant thereof. The compound according to the present invention can be used as a CYP17 enzyme inhibitor, and has better pharmacokinetic parameters, which can improve drug concentration of the compound in an animal, thereby improving the efficacy and safety of the drug, and in turn the compound may be applied in the preparation of the drug for treating CYP17 enzyme-related diseases (such as prostate cancer).
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Paragraph 00861
(2018/11/21)
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- Preparation method of dehydroepiandrosterone
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The invention relates to the technical field of preparation of steroid hormone medicines, and concretely relates to a preparation method of dehydroepiandrosterone. The method comprises the steps of adopting 4-AD as an initiator, and sequentially carrying out acetylation, ketal reduction reaction 'one-pot method' and hydrolysis reaction for preparing the dehydroepiandrosterone, wherein in acetylation, a combination of aluminium trichloride and sulfosalicylic acid or a combination of aluminium trichloride and camphorsulfonic acid is adopted as a catalyst. Compared with the prior art, in the dehydroepiandrosterone product obtained by the invention, the isomers only account for 1 to 3 percent, the mass yield is larger than 88 percent, the refining yield is larger than 78 percent, the product purity is larger than 99 percent, and an industrial application prospect is wide.
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- Inherent steroid 17α,20-lyase activity in defunct cytochrome P450 17A enzymes
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Cytochrome P450 (P450) 17A1 catalyzes the oxidations of progesterone and pregnenolone and is the major source of androgens. The enzyme catalyzes both 17α-hydroxylation and a subsequent 17α,20-lyase reaction, and several mechanisms have been proposed for the latter step. Zebrafish P450 17A2 catalyzes only the 17α-hydroxylations. We previously reported high similarity of the crystal structures of zebrafish P450 17A1 and 17A2 and human P450 17A1. Five residues near the heme, which differed, were changed. We also crystallized this five-residue zebrafish P450 17A1 mutant, and the active site still resembled the structure in the other proteins, with some important differences. These P450 17A1 and 17A2 mutants had catalytic profiles more similar to each other than did the wildtype proteins. Docking with these structures can explain several minor products, which require multiple enzyme conformations. The 17α-hydroperoxy (OOH) derivatives of the steroids were used as oxygen surrogates. Human P450 17A1 and zebrafish P450s 17A1 and P450 17A2 readily converted these to the lyase products in the absence of other proteins or cofactors (with catalytically competent kinetics) plus hydroxylated 17α-hydroxysteroids. The 17α-OOH results indicate that a "Compound I" (FeO3+) intermediate is capable of formation and can be used to rationalize the products. We conclude that zebrafish P450 17A2 is capable of lyase activity with the 17α-OOH steroids because it can achieve an appropriate conformation for lyase catalysis in this system that is precluded in the conventional reaction.
- Gonzalez, Eric,Johnson, Kevin M.,Pallan, Pradeep S.,Phan, Thanh T.N.,Zhang, Wei,Lei, Li,Wawrzak, Zdzislaw,Yoshimoto, Francis K.,Egli, Martin,Peter Guengerich
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p. 541 - 556
(2018/02/14)
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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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- General, Auxiliary-Enabled Photoinduced Pd-Catalyzed Remote Desaturation of Aliphatic Alcohols
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A general, efficient, and site-selective visible light-induced Pd-catalyzed remote desaturation of aliphatic alcohols into valuable allylic, homoallylic, and bis-homoallylic alcohols has been developed. This transformation operates via a hybrid Pd-radical mechanism, which synergistically combines the favorable features of radical approaches, such as a facile remote C-H HAT step, with that of transition-metal-catalyzed chemistry (selective β-hydrogen elimination step). This allows achieving superior degrees of regioselectivity and yields in the desaturation of alcohols compared to those obtained by the state-of-the-art desaturation methods. The HAT at unactivated C(sp3)-H sites is enabled by the easily installable/removable Si-auxiliaries. Formation of the key hybrid alkyl Pd-radical intermediates is efficiently induced by visible light from alkyl iodides and Pd(0) complexes. Notably, this method requires no exogenous photosensitizers or external oxidants.
- Parasram, Marvin,Chuentragool, Padon,Wang, Yang,Shi, Yi,Gevorgyan, Vladimir
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supporting information
p. 14857 - 14860
(2017/10/31)
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- Novel dehydroepiandrosterone benzimidazolyl derivatives as 5α-reductase isozymes inhibitors
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5α-R isozymes (types 1 and 2) play an important role in prostate gland development because they are responsible for intraprostatic dihydrotestosterone (DHT) levels when the physiological serum testosterone (T) concentration is low. In this study, we synthesized seven novel dehydroepiandrosterone derivatives with benzimidazol moiety at C-17, and determined their effect on the activity of 5α-reductase types 1 and 2. The derivatives with an aliphatic ester at C-3 of the dehydroepiandrosterone scaffold induced specific inhibition of 5α-R1 activity, whereas those with a cycloaliphatic ester (cyclopropyl, cyclobutyl, or cyclopentyl ring) or an alcohol group at C-3 inhibited the activity of both isozymes. Derivatives with a cyclohexyl or cycloheptyl ester at C-3 showed no inhibitory activity. In pharmacological experiments, derivatives with esters having an alcohol or the aliphatic group or one of the three smaller cycloaliphatic rings at C-3 decreased the diameter of male hamster flank organs, with the cyclobutyl and cyclopentyl esters exhibiting higher effect. With exception of the cyclobutyl and cyclopentyl esters, these compounds reduced the weight of the prostate and seminal vesicles.
- Arellano, Yazmín,Bratoeff, Eugene,Segura, Tania,Mendoza, Maria Eugenia,Sánchez-Márquez, Araceli,Medina, Yesica,Heuze, Yvonne,Soriano, Juan,Cabeza, Marisa
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p. 908 - 914
(2016/10/09)
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- Synthesis and biological evaluation of 3-tetrazolo steroidal analogs: Novel class of 5α-reductase inhibitors
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In the present study, a series of steroidal tetrazole derivatives of androstane and pregnane have been prepared in which the tetrazole moiety was appended at C-3 and 17a-aza locations. 3-Tetrazolo-3,5-androstadien-17-one (6), 3-tetrazolo-19-nor-3,5-androstadien-17-one (10), 3-tetrazolo-3,5-pregnadien-20-one (14), 17a-substituted 3-tetrazolo-17a-aza-d-homo-3,5-androstadien-17-one (26-31) and 3-(2-acetyltetrazolo)-17a-aza-d-homo-3,5-androstadien-17-one (32) were synthesized from dehydroepiandrosterone acetate (1) through multiple synthetic steps. Some of the synthesized compounds were evaluated for their in vitro 5α-reductase (5AR) inhibitory activity by measuring the conversion of [3H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity also showed a significant reduction (p 50 being 15.6 nM as compared to clinically used drug finasteride (40 nM). There was also a significant inhibition of 5AR-1 with IC50 547 nM compared to finasteride (453 nM).
- Aggarwal, Saurabh,Mahapatra, Manoj Kumar,Kumar, Rajnish,Bhardwaj, Tilak R.,Hartmann, Rolf W.,Haupenthal, J?rg,Kumar, Manoj
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p. 779 - 788
(2016/02/09)
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- Isotope-Labeling Studies Support the Electrophilic Compound i Iron Active Species, FeO3+, for the Carbon-Carbon Bond Cleavage Reaction of the Cholesterol Side-Chain Cleavage Enzyme, Cytochrome P450 11A1
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The enzyme cytochrome P450 11A1 cleaves the C20-C22 carbon-carbon bond of cholesterol to form pregnenolone, the first 21-carbon precursor of all steroid hormones. Various reaction mechanisms are possible for the carbon-carbon bond cleavage step of P450 11A1, and most current proposals involve the oxoferryl active species, Compound I (FeO3+). Compound I can either (i) abstract an O-H hydrogen atom or (ii) be attacked by a nucleophilic hydroxy group of its substrate, 20R,22R-dihydroxycholesterol. The mechanism of this carbon-carbon bond cleavage step was tested using 18O-labeled molecular oxygen and purified P450 11A1. P450 11A1 was incubated with 20R,22R-dihydroxycholesterol in the presence of molecular oxygen (18O2), and coupled assays were used to trap the labile 18O atoms in the enzymatic products (i.e., isocaproaldehyde and pregnenolone). The resulting products were derivatized and the 18O content was analyzed by high-resolution mass spectrometry. P450 11A1 showed no incorporation of an 18O atom into either of its carbon-carbon bond cleavage products, pregnenolone and isocaproaldehyde. The positive control experiments established retention of the carbonyl oxygens in the enzymatic products during the trapping and derivatization processes. These results reveal a mechanism involving an electrophilic Compound I species that reacts with nucleophilic hydroxy groups in the 20R,22R-dihydroxycholesterol intermediate of the P450 11A1 reaction to produce the key steroid pregnenolone.
- Yoshimoto, Francis K.,Jung, I-Ji,Goyal, Sandeep,Gonzalez, Eric,Guengerich, F. Peter
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p. 12124 - 12141
(2016/10/03)
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- Development of a Chemoenzymatic Process for Dehydroepiandrosterone Acetate Synthesis
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Dehydroepiandrosterone (DHEA, 2) is an important endogenous steroid hormone in mammals used in the treatment of a variety of dysfunctions in female and male health,1 as well as an intermediate in the synthesis of steroidal drugs, such as abiraterone acetate which is used for the treatment of prostate cancer.2-4 In this manuscript we describe a novel, concise, and cost-efficient route toward DHEA (2) and DHEA acetate (3) from 4-androstene-3,17-dione (4-AD, 1). Crucial to success was the identification of a ketoreductase from Sphingomonas wittichii for the highly regio- and stereoselective reduction of the C3-carbonyl group of 5-androstene-3,17-dione (5) to the required 3β-alcohol (2, >99% de). The enzyme displayed excellent robustness and solvent stability under high substrate concentrations (up to 150 g/L).
- Fryszkowska, Anna,Peterson, Justine,Davies, Nichola L.,Dewar, Colin,Evans, George,Bycroft, Matthew,Triggs, Neil,Fleming, Toni,Gorantla, Srikanth Sarat Chandra,Hoge, Garrett,Quirmbach, Michael,Timmanna, Upadhya,Reddy Poreddy, Srinivas,Kumar Reddy, D. Naresh,Dahanukar, Vilas,Holt-Tiffin, Karen E.
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p. 1520 - 1528
(2016/08/30)
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- Novel technology for synthesizing epiandrosterone by adopting 4-androstenedione through selective hydrogenation reducing
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The invention provides a novel technology for synthesizing epiandrosterone by adopting 4-androstenedione through selective hydrogenation reducing.Epiandrosterone is synthesized by adopting 4-androstenedione through selective hydrogenation reducing, therefore, the reaction path is greatly shortened, generation of an intermediate reaction by-product is prevented, and the product purity and yield are high; in addition, the reaction raw material consumption is lower, the cost is reduced, and the concept requirement for green production is met.
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Paragraph 0029; 0030; 0031; 0032; 0033; 0034; 0035
(2016/10/09)
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- PROCESSES FOR THE PREPARATION OF DEHYDROEPIANDROSTERONE AND ITS INTERMEDIATES
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The present application relates to a regioselective and stereoselective processes for the preparation of dehydroepiandrosterone (DHEA) and processes for its intermediates.
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Page/Page column 20; 21
(2014/12/12)
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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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- 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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- The 2-(triphenylsilyl)ethoxycarbonyl-("Tpseoc"-) group: A new silicon-based, fluoride cleavable oxycarbonyl protecting group highly orthogonal to the Boc-, Fmoc- and Cbz-groups
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Starting from 2-(triphenylsilyl)ethanol a new oxycarbonyl protecting group cleavable by fluoride ion induced Peterson-elimination has been developed. Known 2-(triphenylsilyl)ethanol has been prepared from commercially available triphenylvinylsilane by a hydroboration-oxidation sequence using the sterically hindered borane reagent 9-BBN. The silyl alcohol was subsequently transformed into its chloroformate, imidazolylcarboxylic acid ester and p-nitrophenyl carbonate and used in standard protocols for the formation of carbamates and carbonates. The Tpseoc group proved to be highly resistant against acidic conditions applied in removal of tert-butyl esters and the t-Boc-group. It also withstood catalytic hydrogenation, treatment with morpholine, methylhydrazine and Pd-reagents/allyl-scavanger combinations, conditions required to cleave Cbz-, Fmoc-, phthalimide- and Alloc-groups. The Tpseoc-group is cleaved upon treatment with TBAF/CsF at 0 °C or r.t. with cleavage times reaching from 10 min. to 24 h. Its orthogonality, ease of cleavage and UV-detectability makes the Tpseoc-group a promising alternative to other widely used silicon based amine protecting groups like the Teoc- and SES-groups.
- Golkowski, Martin,Ziegler, Thomas
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experimental part
p. 4695 - 4718
(2011/08/10)
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- Hydroxylation of steroid compounds by Gelasinospora retispora
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Biotransformation of androst-4-ene-3,17-dione (1), 3β-hydroxypregnan- 5-en-20-one (pregnenolone, 2), 3β-hydroxyandrost-5-en-17-one (DHEA, 3) and estradiol (4) was investigated with fungus of Gelasinospora retispora. Biotransformation of 1 gave 11α-hydroxyandrost-4-ene-3,17-dione (5) in good yield. In the case of compound 2, three compounds, DHEA (3), 3β,17β-dihydroxyandrost-5-ene (6) and 3β,15β- dihydroxyandrost-5-en-17-one (7) were obtained. Moreover, DHEA (3) was converted to 3β,7α-dihydroxyandrost-5-en-17-one (8) and 3β,11α- dihydroxyandrost-5-ene-7,17-dione (9). And it was found that biotransformation of 4 affords 6β-hydroxyestradiol (10).
- Koshimura, Masahiro,Utsukihara, Takamitsu,Hara, Asako,Mizobuchi, Syuhei,Horiuchi, C. Akira,Kuniyoshi, Masayuki
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experimental part
p. 72 - 77
(2010/12/20)
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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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- Studies on Baeyer-Villiger oxidation of steroids: DHEA and pregnenolone d-lactonization pathways in Penicillium camemberti AM83
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Penicillium camemberti AM83 strain is able to carry out effective Baeyer-Villiger type oxidation of DHEA, pregnenolone, androstenedione and progesterone to testololactone. Pregnenolone and DHEA underwent oxidation to testololactone via two routes: through
- Kolek, Teresa,Szpineter, Anna,Swizdor, Alina
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scheme or table
p. 859 - 862
(2009/12/01)
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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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body text
p. 24 - 27
(2009/06/28)
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- Baeyer-Villiger oxidation of DHEA, pregnenolone, and androstenedione by Penicillium lilacinum AM111
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The Baeyer-Villiger monooxygenase (BVMO) produced by Penicillium lilacinum AM111, in contrast to other enzymes of this group known in the literature, is able to process 3β-hydroxy-5-ene steroid substrates. Transformation of DHEA and pregnenolone yielded, as a sole or main product, 3β-hydroxy-17a-oxa-d-homo-androst-5-en-17-one, a new metabolite of these substrates; pregnenolone was transformed also to testololactone. Testololactone was the only product of oxidation of androstenedione by P. lilacinum AM111. Investigations of the time evolution of reaction progress have indicated that the substrates stimulate activity of BVMO(s) of P. lilacinum AM111.
- Kolek, Teresa,Szpineter, Anna,Swizdor, Alina
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experimental part
p. 1441 - 1445
(2009/04/06)
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- DHEA composition and method
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Disclosed are improved pharmaceutical formulations comprising dehydroepiandrosterone (DHEA), enriched in selected polymorphic forms, for therapeutic applications. In one embodiment, the formulation comprises, in solid form, DHEA, at least 85% of which is present as a single polymorph selected from the form I polymorph or the form II polymorph, and at least one pharmaceutical excipient. Methods for making and using such compositions are also disclosed.
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Page/Page column 14
(2008/06/13)
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- METHANESULFONATE SALTS OF ABIRATERONE-3-ESTERS AND RECOVERY OF SALTS OF ABIRATER ONE-3-ESTERS FROM SOLUTION IN METHYL TERT-BUTYL ETHER
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A salt of a compound of formula (I) may be made with methanesulfonic acid. The salt and salts with other acids may be prepared by recovering from methyl tert-butyl ether (MTBE).
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Page/Page column 17-20
(2008/06/13)
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- Synthesis and X-ray crystallographic analysis of 17α-hydroxy-17- methylandrost-4-ene-17-one
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17α-Hydroxy-17-methylandrost-4-ene-17-one is a complex of two steroid molecules with water and its crystal structure has been determined by X-ray crystallographic techniques. The transparent plate-like crystals of this compound crystallized in the orthorhombic space group P212 121, with unit cell parameters: a = 6.382(2), b = 12.841(5), c = 43.350(2) A, λ(Mo Kα) = 0.71073 A, Z = 8. The structure has been solved by direct methods and refined to R = 0.047, wR = 0.086. There are two crystallographically independent molecules, I and II, in the asymmetric unit. In both the molecules, rings A and D adopt a distorted half-chair conformation while rings B and C exist in chair conformation. The crystal structure is stabilized by intermolecular O-H...O and C-H...O hydrogen bonds.
- Verma, Rajnikant,Jasrotia, Dinesh,Bhat, Mousmi
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p. 283 - 287
(2008/02/10)
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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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- Copper-mediated regio- and stereoselective 12β-hydroxylation of steroids with molecular oxygen and an unexpected 12β-chlorination
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It is shown, that copper(I) complexes of 17-(2-iminomethyl)pyridino steroids (17-IMPY steroids) can react with molecular oxygen followed by a regio- and stereoselective γ-hydroxylation in 12β-position. After decomplexation and hydrolysis of the IMPY group 12β-hydroxy-17-ketones are available in practical useful yields. IMPY compounds are simple to prepare by condensation of oxo compounds with (2-aminomethyl)pyridine. In the cases of 17-IMPY steroids the yields in the hydroxylation procedure of an unactivated CH2 group are higher by starting with copper(II) complexes, reduction with benzoin/triethylamine in acetone and reaction with molecular oxygen in comparison to the direct reaction of copper(I) complexes with molecular oxygen in acetone. Employing the procedure in dichloromethane as solvent starting with copper(II) complexes surprisingly the 12β-chloro compound could be isolated next to the hydroxylation product. This regio- and stereoselective γ-chlorination takes place also in acetone, when triethylammonium chloride is added to the reaction mixture. Oxygen is necessary for this reaction. The mechanistic and stereochemical aspects of these new reactions are discussed. Comparison of the different yields of steroids with different A-ring [3-methoxy-estra-1,3,5(10)-triene and 3β-hydroxy-androst-5-ene] pointed out to a subtle influence of the molecular structure far from the reaction centre on these reactions. The successful hydroxylation of the IMPY derivative of 3β-hydroxy-androst-5-ene-17-one shows the tolerance of a homoallylic system against this oxidation procedure. By Oppenauer oxidation 12β-hydroxy- androst-4-ene-3,17-dione is available. The hydroxylation procedure opens a short way to 12β-hydroxy-17-oxo steroids, which are difficult to obtain by other routes. Graphical Abstract.
- Sch?necker, Bruno,Lange, Corinna,Zheldakova, Tatjana,Günther, Wolfgang,G?rls, Helmar,Vaughan, Gavin
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p. 103 - 114
(2007/10/03)
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- Dehydroepiandrosterone (DHEA) congeners for prevention and/or treatment of ulcers
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The present invention is related to acute therapeutic uses of dehydroepiandrosterone (DHEA) congeners. These uses include methods for treating or preventing ulcers which comprise administering to a subject either at risk or in need thereof having an ulcer a therapeutic amount of DHEA congener.
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- Microbial method for hydrolysis and oxidation of androst-5-ene and pregn-5-ene steroid esters
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A microbial method for hydrolysis and oxidation of androst-5-ene and pregn-5-ene steroid esters is disclosed.
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- Use of sigma receptor agonists for the treatment of depression
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Method for the prevention or treatment of depression comprising administering to a steroid-depleted patient suffering therefrom and in need of treatment an effective amount of a sigma 1 receptor agonist.
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- Methods and compositions for attracting and controlling termites
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The present invention provides a composition for attracting termites containing a steroid derivative of formula I The present invention also provides a method for attracting or controlling termites with the composition.
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- N-bromosuccinimide (NBS), an efficient reagent for the conversion of 1,3-oxathiolanes to carbonyl compounds
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Various types of 1,3-oxathiolanes of aromatic and aliphatic carbonyl compounds, including those obtained from α,β-unsaturated aldehydes were efficiently converted to the corresponding carbonyl compounds in the presence of NBS (0.4-0.9 equiv.) under mild reaction conditions. The method was also effectively applied to the chemoselective deprotection of 1,3-oxathiolanes in the presence of 1,3-dioxolanes.
- Karimi,Seradj,Tabaei
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p. 1798 - 1800
(2007/10/03)
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- Method for reducing mast cell mediated allergic reactions
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The present invention is directed to a method for reducing mast cell mediated allergic reactions, including mast cell mediated allergy and asthma. Mast cell mediated allergic reactions, including type I hypersensitivity reasponse to allergens and asthma, are reduced by administering a dehydroepiandrosterone (DHEA) derivative to a patient in a manner which quickly raises blood levels of the active agent.
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- Method for enhancing or accelerating re-epithelialization or re-endothelialization of a tissue
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The present invention is related to a method for enhancing or accelerating re-epithelialization or re-endothelialization of a tissue. Examples of re-epithelialization in which the invention is particularly suited include, but are not limited to, re-epithelialization of (a) skin following surgical wounds, (b) skin abrasions caused by mechanical trauma, caustic agents or burns, (c) cornea following cataract surgery or corneal transplants, (d) mucosal epithelium (respiratory, gastrointestinal, genitourinary, mammary, oral cavity, ocular tissue, liver and kidney) following infection, nonpathological etiologies or drug therapy, (e) skin following grafting and (f) renal tubule following acute tubular necrosis. Examples of re-endothelialization in which the invention is particularly suited include, but are not limited to, re-endothelialization (or regrowth of endothelium) in blood vessels following angioplasty, and the lysis of fibrin clots or lysis or mechanical disruption of thrombi in coronary arteries. In accordance with the present invention, the time to complete re-epithelialization or re-endothelialization is enhanced or accelerated by administering a dehydroepiandrosterone (DHEA) derivative.
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- Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and respiratory distress syndrome
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The present invention is related to a method for preventing or reducing the effects of ischemia. The ischemia may be associated with injury or reperfusion injury, such as occurs as a result of infarctions, thermal injury (bums), surgical trauma, accidental trauma, hemorrhagic shock and the like. The invention is also related to methods for preventing, or reducing bacterial translocation, adult respiratory distress syndrome, adherence of blood cells and platelets to endothelial cells and pulmonary hypertension. In accordance with the present invention, these conditions are prevented or reduced by administering a dehydroepiandrosterone (DHEA) derivative as defined herein.
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- The microbiological hydroxylation of 3α,5-cycloandrostanes by Cephalosporium aphidicola
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The microbiological hydroxylation of some 3α,5-cycloandrostanes by the fungus, Cephalosporium aphidicola has been shown to take place at C-2α and C-14α and a 6β-alcohol was oxidized to the 6-ketone.
- Bensasson, Caroline S.,Hanson, James R.,Le Huerou, Yvan
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p. 1279 - 1282
(2007/10/03)
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- Methods and compositions for attracting and controlling termites
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The present invention provides a composition for attracting termites containing a steroid derivative of formula I The present invention also provides a method for attracting or controlling termites with the composition.
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- The scope and limitations of the reaction of Δ5-steroids with mercury(II) trifluoroacetate
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The effect of the C-3 substituent on the reaction of androst-5-enes with mercury(II) trifluoroacetate in dichloromethane (modified Treibs oxidation) was investigated. 3β-Acyloxyandrost-5-en-17-ones gave 3β-acyloxy-6β- hydroxyandrost-4-en-17-ones accompanied by 3β-acyloxy-6- chloromercuriandrost-5-en-17-ones. 3β-Acetoxy-6β-trifluoroacetoxyandrost- 4-en-17-one and 3β-acetoxy-4β-trifluoroacetoxyandrost-5-en-17-one were revealed to be intermediates in the reaction. The formation of the chloromercury steroids indicated participation in the reaction by the solvent. With 3α-acetoxyandrost-5-en-17-one as substrate, a complete reversal in the product distribution was observed. 3β-Haloandrost-5-en-17- ones gave mainly products that reflected S(N)1 substitution of the halide. 3β-Hydroxy- and 3β-trifluoroacetoxyandrost-5-en-17-ones were formed. 3β- Methoxyandrost-5-en-17-one afforded in nearly identical yields androst-4- ene-3,17-dione, 3β-methoxy-6β-hydroxyandrost-4-en-17-one, 3β-methoxy-6- chloromercuriandrost-5-en-17-one and 6β-hydroxyandrost-4-ene-3,17-dione while androst-5-en-17-one yielded 3β,6β-dihydroxyandrost-4-en-17-one, androst-5-ene-7,17-dione and androst-4-ene-3,17-dione. The effects of solvent and other mercury salts on the reaction were also studied. Treibs oxidation was successful in chloroform, carbon tetrachloride, and dibromomethane, but not in other solvents tested. 3β-Acetoxy-6-bromomercuriandrost-5-en-17-one was obtained in dibromomethane. Replacement of the reagent by mercury(II) trichloroacetate altered the intermediates formed but not the products. Mercury(II) tribromoacetate was unreactive, however.
- Ruddock, Peter L.D.,Williams, David J.,Reese, Paul B.
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p. 650 - 664
(2007/10/03)
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- Reductive cleavage of N,N,N',N'-tetramethylphosphorodiamidate with lithium naphthalenide. A convenient procedure for deoxygenation of alcohols
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A simple, effective alternative procedure has been developed for the reductive cleavage of the N,N,N,'N'-tetramethylphosphorodiamidate group, using lithium naphthalenide as the reagent.
- Liu, Hsing-Jang,Shang, Xiao
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p. 367 - 370
(2007/10/03)
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- Reductive cleavage of benzyl ethers with lithium naphthalenide. A convenient method for debenzylation
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An operationally simple, high-yielding and highly chemoselective procedure has been developed for the conversion of benzyl ethers to the corresponding alcohols, using lithium naphlhalenide as the reagent.
- Liu, Hsing-Jang,Yip, Judy,Shia, Kak-Shan
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p. 2253 - 2256
(2007/10/03)
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- Cleavage of acetals promoted by copper (II) sulphate adsorbed on silica gel
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Copper sulphate supported on silica gel promotes the easy removal of cyclic acetals and tetrahydropyranyl ethers to give the respective parent carbonyl and hydroxyl compounds.
- Cabellero,Gros
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p. 395 - 404
(2007/10/02)
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- The Involvement of an O2-Derived Nucleophilic Species in Acyl-Carbon Cleavage, Catalysed by Cytochrome P-45017α: Implications for Related P-450 Catalysed Fragmentation Reactions
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The postulated iron peroxy species involved in acyl-carbon fission by 17α-hydroxylase-17,20-lyase (P-45017α) was trapped by an aldehyde analogue, partial 9, that was cleaved by the enzyme 10 times faster than the side-chain of the natural substrate 1.
- Robichaud, Peter,Wright, J. Neville,Akhtar, Muhammad
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p. 1501 - 1504
(2007/10/02)
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- Incorporation of Label from 18O2 into Acetate during Side-chain Cleavage Catalysed by Cytochrome P-45017α (17α-hydroxylase-17,20-lyase)
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Samples of pregnenolone and 17α-hydroxypregnenolone deuteriated at the C-21 methyl group have been prepared and subjected to side-chain cleavage with a pig tested microsomal preparation under 18O2. 17α-Hydroxypregnenolone was exclusively cleaved to dehydroisoandrosterone and the acetic acid released during the process was found to incorporate 0.90 atom of 18O.When a similar incubation was performed with pregnenolone two steroidal products, dehydroisoandrosterone and androsta-5,16-dien-3β-ol, were formed in an approximate ratio of 1:2-3 and the acetic acid formed in the process was again shown to contain 0.85 - 0.90 atom of 18O.Complementary experiments in which the two substrates labelled with 18O at the C-20 carbonyl group were incubated under 16O2 gave acetic acid retaining between 65 - 85percent of the original carbonyl oxygen.The experiments strengthen the hypothesis that the two C(17) - C(20) bond cleavages described above correspond to the acyl-carbon fission process of the equation below showing the indicated fate of the various oxygen atoms:
- Akhtar, Muhammad,Corina, David L.,Miller, Sharon L.,Shyadehi, Akbar Z.,Wright, J. Neville
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p. 263 - 268
(2007/10/02)
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- Investigation on Mesityldimethylhalosilanes as Protective Reagents for Alcohols
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The use of mesityldimethylhalosilanes as protecting reagents for steroid alcohols was investigated.The resistance of the obtained silyl ethers was tested in various media.The reaction pathway of the acidic hydrolyses of the silyl ethers is explained.
- Weinzierl, Uwe,Seidel, Wolfgang
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p. 917 - 922
(2007/10/02)
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