- Synthesis of novel pregnane-based 20-carboxamides via palladium-catalysed aminocarbonylation
-
20-Carboxamidopregnene derivatives, such as 3β-acetoxy-5α-pregn-20-ene-20-carboxamides and 5α-pregn-20-ene-20-carboxamides were synthesized from the widely accessible 3β-acetoxy-pregn-5,16-dien-20-one (PDA) using selective hydrogenation, hydrazine and iodoalkene formation, as well as palladium-catalysed aminocarbonylation. The 20-iodo-20-ene derivatives, obtained from the corresponding 20-keto derivatives via their hydrazones, served as substrates. 23 new 20-carboxamides were obtained using various N-nucleophiles ranging from simple primary amines to α-amino acid esters. The novelty of this methodology lies in the application of facile, moderate or high-yielding reactions to obtain otherwise hardly accessible steroidal 20-carboxamides of pharmaceutical importance. In other words, instead of the enzymatic or synthetic degradation of e.g., sterols or cholanic acids, functionalization of the basic skeleton (a ‘building-up’ approach) was used.
- Mikle, Gábor,Zugó, Alexandra,Szatnik, Erzsébet,Maxim, Anita,Mahó, Sándor,Kollár, László
-
p. 1861 - 1867
(2021/01/05)
-
- COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS
-
Provided herein is a compound of Formula I, II, IlIa, IlIb, V, VIa, VIb, VII, VIII, IX, or XI: or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of Formula I, II, IlIa, IlIb, V, VIa, VIb, VII, VIII, IX, or X, and methods of using the compounds, e.g., in the treatment of CNS-related disorders.
- -
-
Paragraph 0579
(2021/01/23)
-
- Predictable Selectivity in Remote C?H Oxidation of Steroids: Analysis of Substrate Binding Mode
-
Predictability is a key requirement to encompass late-stage C?H functionalization in synthetic routes. However, prediction (and control) of reaction selectivity is usually challenging, especially for complex substrate structures and elusive transformations such as remote C(sp3)?H oxidation, as it requires distinguishing a specific C?H bond from many others with similar reactivity. Developed here is a strategy for predictable, remote C?H oxidation that entails substrate binding to a supramolecular Mn or Fe catalyst followed by elucidation of the conformation of the host-guest adduct by NMR analysis. These analyses indicate which remote C?H bonds are suitably oriented for the oxidation before carrying out the reaction, enabling prediction of site selectivity. This strategy was applied to late-stage C(sp3)?H oxidation of amino-steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.
- Olivo, Giorgio,Capocasa, Giorgio,Ticconi, Barbara,Lanzalunga, Osvaldo,Di Stefano, Stefano,Costas, Miquel
-
supporting information
p. 12703 - 12708
(2020/06/02)
-
- PROCESS FOR THE PREPARATION OF 3ALPHA-HYDROXY-5ΑLPHA-PREGNAN-20-ONE (BREXANOLONE)
-
The present invention relates to a new process for the synthesis of 3a-hydroxy-5a-pregnan-20-one, commonly known as brexanolone, wherein the corresponding cyclic 20-ketal or cyclic 20-thioketal compound of formula (IV) is deprotected with the use or iodine in an organic solvent: (I).
- -
-
Page/Page column 12; 13
(2020/06/10)
-
- Selective synthesis of the two main progesterone metabolites, 3α-hydroxy-5α-pregnanolone (allopregnanolone) and 3α-hydroxypregn-4-en-20-one, and an assessment of their effect on proliferation of hormone-dependent human breast cancer cells
-
A directed synthesis of two progesterone metabolites, allopregnanolone and 3a-hydroxy-pregn-4-en-20-one, from Δ16-pregnanolone and progesterone, respectively, was carried out by a reduction of the carbonyl groups in positions 3 and subsequent inversion of the configuration of the resulting alcohols by the Mitsunobu reaction. The selectivity of the reduction of the conjugated carbonyl group in position 3 of progesterone with sodium borohydride in the presence of cerium(III) chloride (Luche reduction) was demonstrated. The ef ect of the obtained metabolites on the proliferation of breast cancer cells of the MCF-7 and T47D lines under normal and steroid-free conditions was studied. It is shown that the ef ect of these compounds on the proliferation depends on the presence of additional steroids in the culture medium. Metabolites exerted small cytostatic ef ects on the growth of the MCF-7 cells under standard conditions, while the transfer of the cells to a steroid-free medium weakened these cytotoxic ef ects. In the experiments with the T47D line cells, the cell growth was stimulated under both standard and steroid-free conditions. Allopregnanolone and progesterone stimulate the growth to a greater extent under steroid-free conditions than under standard ones.
- Kuznetsov, Y. V.,Levina, I. S.,Mikhaevich, E. I.,Scherbakov, A. M.,Tserfas, M. O.,Zavarzin, I. V.
-
p. 552 - 557
(2020/04/21)
-
- NEUROSTEROID COMPOUNDS AND METHODS FOR THEIR PREPARATION AND USE IN TREATING CENTRAL NERVOUS SYSTEM DISORDERS
-
Described herein is the chemical structure of neurosteroid derivative compounds, methods of synthesizing the derivatives, and their uses in treating disorders, including those of the central nervous system. These compounds are readily synthesized and have improved pharmaceutical properties, including water solubility, compared to known neurosteroids.
- -
-
Paragraph 0103; 0105; 0106
(2019/11/12)
-
- OXYSTEROLS AND METHODS OF USE THEREOF
-
Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R2, R3, R4, R5, and and R6 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
- -
-
Paragraph 00332; 00333
(2018/05/16)
-
- Steroid compound 3-site hydroxyl configuration inversion method
-
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.
- -
-
-
- COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS
-
Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein (II), A, R1, R2, R3a, R4a, R4b, R5, R7a, and R7b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.
- -
-
Page/Page column 117
(2016/05/24)
-
- DERIVATIVES OF ALLOPREGNANOLONE AND OF EPIALLOPREGNANOLONE AND USES THEREOF FOR TREATING A NEUROPATHOLOGICAL CONDITION
-
The présent invention relates to novel neurosteroids, especially derivatives of allopregnanolone and of epiallopregnanolone of formula (I) and the uses thereof as médicament for the treatment of neuropathologies, in particular neuropathies induced by the chemotherapy of a cancer. Thèse molécules according to the invention have both preventative and curative effects. The neurosteroids according to the invention may also be of use in the treatment of neurodegenerative disorders, in particular for preventing neuronal cell death. They may thus be used as neuroprotectants and/or as an agent that stimulates neuronal prolifération.
- -
-
-
- Unraveling the structure-activity relationship of tomatidine, a steroid alkaloid with unique antibiotic properties against persistent forms of Staphylococcus aureus
-
Staphylococcus aureus (S. aureus) is responsible for difficult-to-treat and relapsing infections and constitutes one of the most problematic pathogens due to its multiple resistances to clinically available antibiotics. Additionally, the ability of S. aureus to develop small-colony variants is associated with a reduced susceptibility to aminoglycoside antibiotics and in vivo persistence. We have recently demonstrated that tomatidine, a steroid alkaloid isolated from tomato plants, possesses anti-virulence activity against normal strains of S. aureus as well as the ability to potentiate the effect of aminoglycoside antibiotics. In addition, tomatidine has shown antibiotic activity against small-colony variants of S. aureus. We herein report the first study of the structure-activity relationship of tomatidine against S. aureus.
- Chagnon, Félix,Guay, Isabelle,Bonin, Marc-André,Mitchell, Gabriel,Bouarab, Kamal,Malouin, Fran?ois,Marsault, éric
-
p. 605 - 620
(2014/06/23)
-
- Synthesis of steroidal derivatives containing substituted, fused and spiro pyrazolines
-
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
-
-
- Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity
-
In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)1 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and α-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5α/β-dihydro-C19/C21/C24-steroids into the corresponding 3β-hydroxysteroids, showing Km of 1.3-9.1 μM and kcat of 1.1-7.6 min-1. The stereospecific reduction was also observed in the metabolism of 5α- and 5β- dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3β-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate.
- Endo, Satoshi,Matsunaga, Toshiyuki,Kumada, Sho,Fujimoto, Airi,Hara, Akira,Ohno, Satoshi,El-Kabbani, Ossama,Hu, Dawei,Toyooka, Naoki,Mano, Jun'Ichi,Tajima, Kazuo
-
p. 23 - 30,8
(2020/08/20)
-
- Novel steroid inhibitors of glucose 6-phosphate dehydrogenase
-
Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially developed; the 3β-alcohol can be replaced with 3β-H-bond donors such as sulfamide, sulfonamide, urea, and carbamate. Improved potency was achieved by replacing the androstane nucleus with a pregnane nucleus, provided a ketone at C-20 is present. For pregnan-20-ones incorporation of a 21-hydroxyl group is often beneficial. The novel compounds generally have good physicochemical properties and satisfactory in vitro DMPK parameters. These derivatives may be useful for examining the role of G6PD inhibition in cells and will assist the future design of more potent steroid inhibitors with potential therapeutic utility.
- Hamilton, Niall M.,Dawson, Martin,Fairweather, Emma E.,Hamilton, Nicola S.,Hitchin, James R.,James, Dominic I.,Jones, Stuart D.,Jordan, Allan M.,Lyons, Amanda J.,Small, Helen F.,Thomson, Graeme J.,Waddell, Ian D.,Ogilvie, Donald J.
-
supporting information; experimental part
p. 4431 - 4445
(2012/09/11)
-
- STEROID ALKALOIDS AND USES THEREOF AS ANTIMICROBIAL AGENTS AGAINST ELECTRON TRANSPORT-DEFICIENT MICROBES AND AS POTENTIATORS FOR ANTIMICROBIAL AGENTS AGAINST PATHOGENIC BACTERIA
-
The present invention includes novel compounds based on the tomatidine skeleton as well as composition comprising these compounds alone and in combination with known compounds, which exhibit antimicrobial activity against extracellular or intracellular electron transport-deficient microbes and/or increase the antimicrobial activity of aminoglycoside antibiotics against their targets, and which are useful as antibacterial agents for treatment or prophylaxis of monomicrobiotic or polymicrobic bacterial infections or for the reduction of antibiotic resistance development in animals or in humans, or for use as antiseptics or agents for sterilization or disinfection.
- -
-
Page/Page column 92-93
(2012/09/10)
-
- PROGESTERONE RECEPTOR ANTAGONISTS AND USES THEREOF
-
The present invention relates to a compound of formula (I): for its use as progesterone receptor antagonist, in particular for its use for the prevention and/or the treatment of cancer or uterine pathologies.
- -
-
Page/Page column 59
(2011/11/30)
-
- Stereoselective synthesis and antimicrobial activity of steroidal C-20 tertiary alcohols with thiazole/pyridine side chain
-
Stereoselective synthesis of novel steroidal C-20 tertiary alcohols with thiazole and pyridine side chain using Grignard reaction of steroidal ketones and thiazole/pyridine magnesium bromide have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compounds exhibited significant antifungal and antibacterial activity against all the tested strains.
- Shingate, Bapurao B.,Hazra, Braja G.,Salunke, Deepak B.,Pore, Vandana S.,Shirazi, Fazal,Deshpande, Mukund V.
-
p. 3681 - 3689
(2011/11/06)
-
- Stereospecific reduction of 5β-reduced steroids by human ketosteroid reductases of the AKR (aldo-keto reductase) superfamily: Role of AKR1C1-AKR1C4 in the metabolism of testosterone and progesterone via the 5β-reductase pathway
-
Active sex hormones such as testosterone and progesterone are metabolized to tetrahydrosteroids in the liver to terminate hormone action. One main metabolic pathway, the 5β-pathway, involves 5β-steroid reductase (AKR1D1, where AKR refers to the aldo-keto reductase superfamily), which catalyses the reduction of the 4-ene structure, and ketosteroid reductases (AKR1C1-AKR1C4), which catalyse the subsequent reduction of the 3-oxo group. The activities of the four human AKR1C enzymes on 5β-dihydrotestosterone, 5β-pregnane-3,20-dione and 20α-hydroxy-5β-pregnan-3-one, the intermediate 5β-dihydrosteroids on the 5β-pathway of testosterone and progesterone metabolism, were investigated. Product characterization by liquid chromatography-MS revealed that the reduction of the 3-oxo group of the three steroids predominantly favoured the formation of the corresponding 3α-hydroxy steroids. The stereochemistry was explained by molecular docking. Kinetic properties of the enzymes identified AKR1C4 as the major enzyme responsible for the hepatic formation of 5β-tetrahydrosteroid of testosterone, but indicated differential routes and roles of human AKR1C for the hepatic formation of 5β-tetrahydrosteroids of progesterone. Comparison of the kinetics of the AKR1C1-AKR1C4-catalysed reactions with those of AKR1D1 suggested that the three intermediate 5β-dihydrosteroids derived from testosterone and progesterone are unlikely to accumulate in liver, and that the identities and levels of 5β-reduced metabolites formed in peripheral tissues will be governed by the local expression of AKR1D1 and AKR1C1-AKR1C3. The Authors Journal compilation 2011 Biochemical Society.
- Jin, Yi,Mesaros, A. Clementina,Blair, Ian A.,Penning, Trevor M.
-
experimental part
p. 53 - 61
(2012/06/15)
-
- METHODS OF NEUROPROTECTION USING NEUROPROTECTIVE STEROIDS AND A VITAMIN D
-
Described herein are compositions and methods for treating or preventing nervous system injury. In particular, the methods and compositions relate to the use of at least one neuroprotective steroid, such as progesterone, and vitamin D.
- -
-
-
- Development and screening of water-soluble analogues of progesterone and allopregnanolone in models of brain injury
-
Preclinical and clinical research findings have revealed that the hormone progesterone, when acutely administered, can dramatically reduce cerebral edema, inflammation, tissue necrosis, and programmed cell death following traumatic brain injury (TBI). The poor aqueous solubility of progesterone, however, limits its potential use as a therapeutic. Several chemically novel analogues of progesterone and its natural metabolite allopregnanolone have been synthesized and screened using both in vitro and whole animal models of TBI. The new derivatives demonstrated greatly improved solubility and select compounds have shown equivalent effectiveness to progesterone in reducing cerebral edema after TBI. 2009 American Chemical Society.
- MacNevin, Christopher J.,Atif, Fahim,Sayeed, Iqbal,Stein, Donald G.,Liotta, Dennis C.
-
experimental part
p. 6012 - 6023
(2010/02/28)
-
- STEROID ANALOGUES FOR NEUROPROTECTION
-
Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.
- -
-
Page/Page column 121-122
(2009/10/21)
-
- Δ5-3β-hydroxysteroid dehydrogenase (3βHSD) from Digitalis lanata. Heterologous expression and characterisation of the recombinant enzyme
-
During the biosynthesis of cardiac glycosides, Δ5-3β- hydroxysteroid dehydrogenase (3βHSD, EC 1.1.1.51) converts pregnenolone (5-pregnen-3β-ol-20-one) to isoprogesterone (5-pregnene-3,20-dione). A 3βHSD gene was isolated from leaves of Digitalis lanata. It consisted of 870 nucleotides containing a 90 nucleotide long intron. A full-length cDNA clone that encodes 3βHSD was isolated by RT-PCR from the same source. A Sph I/Kpn I 3βHSD cDNA was cloned into the pQE30 vector and then transferred into E. coli strain M15[pREP4]. 3βHSD cDNA was functionally expressed as a His-tagged fusion protein (pQ3βHSD) composed of 273 amino acids (calculated molecular mass 28,561 Da). PQ3βHSD was purified by metal chelate affinity chromatography on Ni-NTA. Pregnenolone and other 3β-hydroxypregnanes but not cholesterol were 3β-oxidised by pQ3βHSD when NAD was used as the co-substrate. Testosterone (4-androsten-17β-ol-3-one) was converted to 4-androstene-3,17-dione indicating that the pQ3βHSD has also 17β-dehydrogenase activity. pQ3βHSD was able to reduce 3-keto steroids to their corresponding 3β-hydroxy derivatives when NADH was used as the co-substrate. For comparison, 3βHSD genes were isolated and sequenced from another 6 species of the genus Digitalis. Gene structure and the deduced 3βHSD proteins share a high degree of similarity. Georg Thieme Verlag KG Stuttgart.
- Herl, Vanessa,Frankenstein, Joerdis,Meitinger, Nadine,Mueller-Uri, Frieder,Kreis, Wolfgang
-
p. 704 - 710
(2008/03/12)
-
- Stereoselective syntheses of 20-epi cholanic acid derivatives from 16-dehydropregnenolone acetate
-
A stereoselective total synthesis of naturally occurring 20-epi cholanic acid derivatives has been realized, starting from readily available 16-dehydropregnenolone acetate. The key step of these syntheses involves an ionic hydrogenation of a C-20,22-ketene dithioacetal and deoxygenation of steroidal C-20 tert-alcohols, to set up the unnatural C(20R) configuration with 100% stereoselectivity. The unnatural C-22 aldehydes with C(20R) stereocenters thus obtained were elaborated to 20-epi cholanic acid derivatives. Two derivatives of 20-epi cholanic acid were synthesized and their structures have been confirmed by single crystal X-ray analysis. Catalytic hydrogenation of 16-dehydropregnenolone acetate and 16-dehydropregnenolone in ethanol affords C-5,C-16 tetrahydro products. Crystal structure analysis of one of these products revealed C-5α and C-17α configurations of the hydrogen atoms.
- Shingate, Bapurao B.,Hazra, Braja G.,Pore, Vandana S.,Gonnade, Rajesh G.,Bhadbhade, Mohan?M.
-
p. 5622 - 5635
(2008/01/06)
-
- Synthesis of 3α-hydroxy-21-(1′-imidazolyl)-3β-methoxyl- methyl-5α-pregnan-20-one via lithium imidazole with 17α- acetylbromopregnanone
-
The synthesis of biologically active 3α-hydroxyl-21-(1′- imidazolyl)-3β-methoxymethyl-5α-pregnan-20-one (11) was accomplished in six steps. The key steps were the improvement of stereoselectivity for acetyl isomers in C-17 and the introduction of imidazole into the core structure by use of lithium imidazole. This latter key step provided the desired product 11 in 82% yield without the formation of 1,3-disubstituted imidazolium salt as impurity, which is generally observed in traditional method.
- Wong, Fung Fuh,Chen, Chun-Yen,Chen, Tse-Hsin,Huang, Jiann-Jyh,Fang, Hsiao-Ping,Yeh, Mou-Yung
-
-
- Stereoselective syntheses of unnatural steroidal C(20R) aldehydes by ionic hydrogenation of C-20 tertiary alcohols
-
Syntheses of three unnatural steroidal C(20R) aldehydes have been realised from 16-dehydropregnenolone acetate. The salient feature of the synthesis is the ionic hydrogenation of C-20 tertiary alcohols leading to the formation of the C(20R) unnatural isomer with complete stereoselectivity. Oxidative hydrolysis of the dithiane moiety furnished the C(20R) aldehydes.
- Shingate, Bapurao B.,Hazra, Braja G.,Pore, Vandana S.,Gonnade, Rajesh G.,Bhadbhade, Mohan M.
-
p. 9343 - 9347
(2007/10/03)
-
- Reduction of steroidal ketones with amine - Boranes
-
Complexes of secondary amines with borane, R2NH·BH 3, surpass sodium borohydride as reducing agents for saturated and unsaturated steroidal 3-, 12-, 17-, and 20-ketones as regards chemo- and regioselectivity and mildness of the reaction conditions. In the case of 12-ketones, stereoselectivity is also improved.
- Leontjev,Vasiljeva,Pivnitsky
-
p. 703 - 708
(2007/10/03)
-
- Cerium ammonium nitrate: A new catalyst for regioselective protection of glycols
-
The regioselective introduction of a methoxymethyl (MOM) group on different type of glycols via an orthoester intermediate was investigated. The novelty presented in this study is the use of ceric ammonium nitrate instead of the previously employed camphorsulfonic acid as catalyst. The monoprotection reaction was revealed to be highly selective when the glycol moiety was in the presence of an ether functionality. Graphical abstract
- Comin, María J.,Elhalem, Eleonora,Rodriguez, Juan B.
-
p. 11851 - 11860
(2007/10/03)
-
- Steroid transformations with Exophiala jeanselmei var. lecanii-corni and Ceratocystis paradoxa
-
The fungi Exophiala jeanselmei var. lecanii-corni [IMI (International Mycological Institute) 312989, UAMH (University of Alberta Microfungus Collection and Herbarium) 8783] and Ceratocystis paradoxa (IMI 374529, UAMH 8784) have been examined for their potential in steroid biotransformation. The study has determined that E. jeanselmei var. lecanii-corni effected overall anti-Markovnikov hydration on dehydroisoandrosterone, and side-chain degradation on a variety of pregnanes. Both ascomycetes were found to carry out redox reactions of alcohols and ketones as well as 1,4 reduction of α,β-unsaturated carbonyl systems.
- Porter, Roy B.R.,Gallimore, Winklet A.,Reese, Paul B.
-
p. 770 - 779
(2007/10/03)
-
- Biotransformations of progesterone by Chlorella spp.
-
Thirty-eight strains of Chlorella spp. were used as bioreactors on progesterone. Fourteen strains were ineffective whilst the others biotransformed the substrate. The observed bioreactions for progesterone were the hydroxylation, the reduction and the side-chain degradation. The kinds of biotransformation seem to fit the actual classification of the strains.
- Pollio, Antonino,Pinto, Gabriele,Della Greca, Marina,Fiorentino, Antonio,Previtera, Lucio
-
p. 685 - 688
(2007/10/03)
-
- Selective 1-Dehydrogenation of Progesterone by Aspergillus fumigatus
-
Fermentation of progesterone with acetone-dried cells of Aspergillus fumigatus in the presence of β-cyclodextrin yields pregna-1,4-diene-3,20-dione as the single isolable product.
- Garai, Subhadra,Banerjee, Sukdeb,Mahato, Shashi B.
-
p. 408 - 409
(2007/10/03)
-
- Sodium-retaining activity of some natural and synthetic 21-deoxysteroids
-
The effect of progesterone and six other C21 -deoxysteroids on renal sodium retention by male adrenaleotomized rats was compared with the effect exerted by the natural corticoids aldosterone, 11-deoxycorticosterone, and corticosterone. Steroids were active in the following order: aldosterone > 11,19-oxidoprogesterone > 5αH-3,20-pregnanedione ≥ 5βH-3,20-pregnanedione > progesterone = 11-ketoprogesterone > 6,19-oxidoprogesterone = 11-keto- 6,19-oxidoprogesterone ≥ corticosterone. All C21-deoxysteroids, except 11,19-oxidoprogesterone, exhibited parabolic log dose-response functions, indicating an effect that opposes renal sodium retention at high doses. 11,19-Oxidoprogesterone and the natural corticoids exhibited normal, exponential, log dose-response curves. Diverse geometric parameters related to molecular planarity were calculated and their correlation with biopharmacological properties was attempted. The best linear regression was obtained for correlation of the concavity of log dose-response parabolas (second-order coefficients) of C21-deoxysteroids with the C3=O/ring D angle of these molecules. A good linear regression could also be obtained for correlation of the affinity of C21-deoxysteroids, except 11,19- oxidoprogesterone, for purified type I mineralocorticoid receptors with those angles. The latter correlation deteriorated upon incorporation of the affinity data for the three natural corticoids, due to similar affinities of these hormones for type I mineralocorticoid receptors, but could be restored when the binding data for the unpurified, corticosterone-binding globulin- containing stage of the receptors were considered. In vivo binding data followed the same trend as that for unpurified receptors.
- Burton,Galigniana,De Lavallaz,Brachet-Cota,Sproviero,Ghini,Lantos,Damasco
-
p. 535 - 543
(2007/10/03)
-
- METHODS, COMPOSITIONS, AND COMPOUNDS FOR ALLOSTERIC MODULATION OF THE GABA RECEPTOR BY MEMBERS OF THE ANDROSTANE AND PREGNANE SERIES
-
Method, compositions, and compounds for modulating brain excitability to alleviate stress, anxiety, insomnia and seizure activity using certain steroid derivatives that act at a newly identified site on the gamma-aminobutyric acid receptor-chloride ionophore (GR) complex.
- -
-
-
- Oxygen-functionalization of C13-angular methyl group in pregnane steroid by means of intramolecular carbony-mediated anodic oxidation
-
An oxygen-functionalization of the C13-angular methyl group in 3β-acetoxy-5α-pregnan-20-one and its tetra-O-acetyl-β-D-glucopyranosyl derivative has been effected by means of an anodic oxidation mediated by the C20-carbonyl residue in the steroid skeleton.
- Shibuya,Murakami,Shimada,Yoshikawa,Kitagawa
-
p. 1143 - 1147
(2007/10/02)
-
- 5 α-pregnan-20-ones and 5-pregnen-20-ones and related compounds
-
Compounds of the formulae: STR1 useful as anti-obesity, anti-diabetic, anti-coronary and hypolipidemic agents.
- -
-
-
- Cerium(IV)-Mediated Synthesis of Tetrahydrofuranyl Ethers
-
The reaction of tetrahydrofuran with an alcohol in the presence of ceric triethylammonium nitrate provides a convenient and general procedure for protecting the hydroxyl function.Tetrahydrofuranyl ethers of primary, secondary and tertiary alcohols were obtained in good yields.
- Maione, Anna M.,Romeo, A.
-
p. 250 - 251
(2007/10/02)
-
- REGIOSELECTIVE REDUCTION OF POLYKETONES ON SILICA GEL SURFACE WITH BORANE-TRIMETHYLAMINE COMPLEX
-
Steroidal diones and trione, bicyclic diones (7 and 8) and a tricyclic dione were adsorbed on silica gel and reduced with BH3*NMe3.The carbonyl groups at C-3 of the steroids, at C-4 of 7 and at C-3 of 8 were reduced regioselectively.The FT-IR spectra of 5α- and 5β-androstane-3,17-dione adsorbed on silica gel were measured.
- Gohzu, Shun-ichi,Tada, Masahiro
-
-
- Steroids. Part 21. Photorearrangement of Steroidal Nitronate Salts and a N-Butyl Spiro-oxaziridine
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Irradiation, at 254 nm, of ethanol solutions of nitro-steroids in the presence of an excess of sodium ethoxide gave a range of products including hydroxamic acids, ketones, and alkenes possibly derived from the anions of the N-hydroxyoxaziridines.Alternatively, the ketones and hydroxamic acids may be derived from the anions of the hydroxy-nitroso compounds.The proportions of products depend on the ring size and stereochemistry and the photoreactions differ significantly from those observed for N-alkyl spiro-oxaziridines including a steroidal N-butyl spiro-oxaziridine.
- Edge, Graham J.,Imam, Syed H.,Marples, Brian A.
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p. 2319 - 2326
(2007/10/02)
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- STUDY OF THE DIRECT EFFECT OF LHRH AGONIST ON TESTICULAR 17-HYDROXYLASE AND 5α-REDUCTASE ACTIVITIES IN NON-HYPOPHYSECTOMIZED ADULT RATS TREATED WITH AN ANTI-LUTEINIZING HORMONE SERUM
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In order to study both direct and pituitary-mediated mechanisms of action of the LHRH analogue 6, des-Gly-NH210>LHRH ethylamide upon testicular steroidogenesis in adult rat, we compared the effects of the agonist when administered alone or concomitantly with an anti-LH serum to non-hypophysectomized rats.Testicular steroid contents and in vitro progesterone and testosterone metabolism were determined.Anti-LH serum administration was able to prevent 5α-reductase stimulation by the agonistic peptide, but not the inhibition of 17-hydroxylase activity.These data suggest that modulation of 17-hydroxylase involves both direct and pituitary-mediated processes, while 5α-reductase stimulation is mainly if not only due to a pituitary-mediated mechanism.
- Carmichael, Rejean,Belanger, Alain
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- METABOLISM AND CONJUGATION OF PROGESTERONE BY BOVINE LIVER AND ADIPOSE TISSUES, IN VITRO
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The ability of bovine liver and fat to metabolize progesterone and also to form glucuronide conjugates with these progestins in vitro was investigated.Tissue supernatants were incubated with progesterone, UDP-glucuronic acid, and a NADPH generating system for 5 hr, at 37 deg C.Steroids were identified by thin-layer chromatography, high performance liquid chromatography, and recrystallization to a constant specific activity.The total original radioactivity which could not be removed by exhaustive ether extraction (presumptive conjugates) was 44.7 +/- 14.2percent in liver, 5.0 +/- 3.6percent in subcutaneous fat, and 3.7 +/- 2.2percent in kidney fat samples.Progestins identified in liver samples include 5β-pregnane-3α,20α-diol (free and conjugate), 5β-pregnane-3α,20β-diol (free and conjugate), 3α-hydroxy-5β-pregnan-20-one (free and conjugate), 3β-hydroxy-5β-pregnan-20-one (free), 5β-pregnane-3,20-dione (free), and progesterone (conjugate).Progestins identified in both the free and conjugate fractions of subcutaneous fat and kidney fat samples include progesterone, 3α-hydroxy-5β-pregnan-20-one, 20β-hydroxy-4-pregnen-3-one, and 20α-hydroxy-4-pregnen-3-one.Differences due to sex of bovine used were noted.These results confirm the ability of bovine liver to readily metabolize progesterone and form glucuronide conjugates of these compounds and suggest that adipose tissues take an active role in these actions in cattle.
- Clemens, J. D.,Estergreen, V. L.
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p. 287 - 306
(2007/10/02)
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- Metabolism and Effects of Progesterone in the Human Endometrial Adenocarcinoma Cell Line HEC-1
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Human endometrial adenocarcinoma cells (HEC-1 line) were incubated with 14C-progesterone.Four major labeled metabolites, 3β-hydroxy 5α-pregnan-20-one, 5α-pregnane-3β,20α-diol, 20α-hydroxy-4-pregnen-3-one and 5α-pregnane-3,20-dione were separated by thin layer chromatography, further purified by high pressure liquid chromatography, and finally identified by addition of carriers and crystallization to constant specific activity.Among these metabolites, 5α-pregnane-3β,20α-diol seems characteristic of this cell line since its formation from labeled progesterone was not detected in normal endometrium or in 2 specimens of endometrial adenocarcinoma.The growth of HEC cells was unaffected by either progesterone or medroxyprogesterone acetate, a slowly metabolized progestin, at about 10-6 M levels but was inhibited by about 10-5 M concentrations of these compounds.
- Satyaswaroop, P. G.,Frost, A.,Gurpide, E.
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- TOTAL SYNTHESIS OF (+)-5α-DIHYDROPREGNENOLONE VIA ACETYLENE-CATION CYCLIZATION
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The stereoselective total synthesis of (+)-5α-dihydropregnenolone 7 via acetylene-cation cyclization of 6, which was readily prepared from the optically active D-ring aromatic steroid 1, is described.
- Kametani, Tetsuji,Suzuki, Koji,Nemoto, Hideo
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p. 1469 - 1470
(2007/10/02)
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- Efficient Synthesis of a Pregnane-type Steroid. Total Synthesis of (+)-5α-Dihydropregnenolone
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An efficient total synthesis of the title compound (7) was carried out by acetylene-cation cyclisation of a 1-(pent-3-ynyl)perhydro-2-phenanthrol (6) which was prepared from a ring-D-aromatic steroid (1) via Eschenmoser ring-opening of its 13,17a-epoxy-17-oxo-derivative (3).
- Kametani, Tetsuji,Suzuki, Koji,Nemoto, Hideo
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p. 2805 - 2807
(2007/10/02)
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