![(3R,5S,8R,9S,10S,13S,14S)-10,13-Dimethyl-3-(tetrahydro-furan-2-yloxy)-hexadecahydro-cyclopenta[a]phenanthren-17-one](/Databaselist/images/loading.webp)
53-41-8Relevant academic research and scientific papers
Cloning, characterization, and expression analysis of a putative 17 beta-hydroxysteroid dehydrogenase 11 in the abalone, Haliotis diversicolor supertexta
Zhai, Hong-Ning,Zhou, Jin,Cai, Zhong-Hua
, p. 57 - 63 (2012)
The 17-beta-hydroxysteroid dehydrogenases (17β-HSDs) are key enzymes for sex steroid biosynthesis. To date, relatively little is known about the presence and function of 17β-HSDs in marine gastropods. In the present study, a cDNA sequence encoding putative 17β-HSD type 11 (17β-HSD-11) was identified in marine abalone (Haliotis diversicolor supertexta). The full-length cDNA contains 1058 bp, including an open reading frame (ORF) of 900 bp that encodes a protein of 299 amino acids. Comparative structural analysis revealed that abalone 17β-HSD-11 shares relatively high homology with other 17b-HSD-11 hormologues, and a lesser degree of amino acid identity with other forms of 17b-HSD, especially in the functional domains, including the cofactor binding domain (TGxxxGxG) and catalytic site (YxxSK). Phylogenetic analysis showed that abalone 17β-HSD-11 belongs to the short-chain dehydrogenase/reductase (SDR) family. Functional analysis following transient transfection of the ORF into human embryonic kidney-293 (HEK-293) cells indicated that abalone 17β-HSD-11 has the ability to convert 5α-androstane-3α,17β-diol (3α-diol) to androsterone (A) and testosterone (T) to androstenedione (4A). Expression analysis in vivo demonstrated that abalone 17β-HSD-11 is differentially expressed during three stages (non-reproductive, reproductive, and post-reproductive). Taken together, these results indicate that ab-17β-HSD-11 is an SDR family member with a potential role in steroid regulation during the reproductive stage.
Convenient stereoselective synthesis of some 3-aminosteroid scaffolds
Solum, Eirik Johansson,Mohamed, Yasser Mahmoud A.
, p. 1159 - 1164 (2019)
An efficient stereoselective synthesis 3α- and 3β-aminoandrostan-17-one and 3α-amino dehydroepiandrosten-17-one based on a Mitsunobu reaction has been developed, using azide as the ammonia equivalent. All the products were isolated in high yield.
Photoinduced Deoxygenative Borylations of Aliphatic Alcohols
Wu, Jingjing,B?r, Robin M.,Guo, Lin,Noble, Adam,Aggarwal, Varinder K.
, p. 18830 - 18834 (2019/11/22)
A photochemical method for converting aliphatic alcohols into boronic esters is described. Preactivation of the alcohol as a 2-iodophenyl-thionocarbonate enables a novel Barton–McCombie-type radical deoxygenation that proceeds efficiently with visible light irradiation and without the requirement for a photocatalyst, a radical initiator, or tin or silicon hydrides. The resultant alkyl radical is intercepted by bis(catecholato)diboron, furnishing boronic esters from a diverse range of structurally complex alcohols.
Catalytic removal of tert-butyldimethylsilyl (TBS) ether by PVP-I
Ke, Yanxiong,Lu, Guangying,Ren, Jiangmeng,Wang, Di,Zeng, Bu-Bing
, (2019/09/06)
A mild, efficient and rapid protocol the deprotection of alcoholic TBDMS ethers using PVP-1 as catalyst in methanol, the procedure of deprotection of various TBDMS ethers were found to be very convenient, easy work-up, high yielding.
Steroid compound 3-site hydroxyl configuration inversion method
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Paragraph 0025; 0030; 0031, (2018/12/14)
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.
Stereo selective one-step reduction in the steroid skeleton 4 - ene -3 - ketone as a 3 α - hydroxy - 5 β - hydrogen A/B cis structure method
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Paragraph 0022; 0041; 0042; 0043, (2017/02/17)
The invention relates to a method for one-step reduction of a 4-ene-3-one structure in a steroid skeleton into an A/B cis-3a-hydroxy-5b-hydrogen structure, belonging to the fields of organic chemistry and drug synthesis. According to the method, under the conditions of room temperature and an environment of absolute ethyl alcohol, cuprous chloride is used as a catalyst and sodium borohydride is used as a reducing agent for high-selectivity conversion of the 4-ene-3-one structure of 4-AD, ADD and derivatives thereof into the A/B cis-3a-hydroxy-5b-hydrogen structure. According to results of X-diffraction results, an androstane-3a-hydroxy-5b-hydrogen-17-one product prepared by using the method has a stereo structure; reaction conditions are mild and simple; used reagents are cheap and easily available; operation is convenient; good repeatability is realized, and high yield is obtained. The method provided by the invention lays a good foundation for exploitation of resourceful utilization of sterol and for research on synthesis of drugs like ursodesoxycholic acid, chenodeoxycholic acid, deoxycholic acid and ecdyson with the A/B cis-structure with non-cholic acid type steroids as raw materials.
Aldo-keto Reductase 1B15 (AKR1B15): A mitochondrial human aldo-keto reductase with activity toward steroids and 3-keto-acyl-CoA conjugates
Weber, Susanne,Salabei, Joshua K.,M?ller, Gabriele,Kremmer, Elisabeth,Bhatnagar, Aruni,Adamski, Jerzy,Barski, Oleg A.
, p. 6531 - 6545 (2015/03/30)
Alto-keto reductases (AKRs) comprise a superfamily of proteins involved in the reduction and oxidation of biogenic and xenobiotic carbonyls. In humans, at least 15 AKR superfamily members have been identified so far. One of these is a newly identified gene locus, AKR1B15, which clusters on chromosome 7 with the other human AKR1B subfamily members (i.e. AKR1B1 and AKR1B10). We show that alternative splicing of the AKR1B15 gene transcript gives rise to two protein isoforms with different N termini: AKR1B15.1 is a 316-amino acid protein with 91% amino acid identity to AKR1B10; AKR1B15.2 has a prolonged N terminus and consists of 344 amino acid residues. The two gene products differ in their expression level, subcellular localization, and activity. In contrast with other AKR enzymes, which are mostly cytosolic, AKR1B15.1 co-localizes with the mitochondria. Kinetic studies show that AKR1B15.1 is predominantly a reductive enzyme that catalyzes the reduction of androgens and estrogens with high positional selectivity (17β-hydroxysteroid dehydrogenase activity) as well as 3-ketoacyl-CoA conjugates and exhibits strong cofactor selectivity toward NADP(H). In accordance with its substrate spectrum, the enzyme is expressed at the highest levels in steroid-sensitive tissues, namely placenta, testis, and adipose tissue. Placental and adipose expression could be reproduced in the BeWo and SGBS cell lines, respectively. In contrast, AKR1B15.2 localizes to the cytosol and displays no enzymatic activity with the substrates tested. Collectively, these results demonstrate the existence of a novel catalytically active AKR, which is associated with mitochondria and expressed mainly in steroid-sensitive tissues.
Characterization of hamster NAD+-dependent 3(17)β-hydroxysteroid dehydrogenase belonging to the aldo-keto reductase 1C subfamily
Endo, Satoshi,Noda, Misato,Ikari, Akira,Tatematsu, Kenjiro,El-Kabbani, Ossama,Hara, Akira,Kitade, Yukio,Matsunaga, Toshiyuki
, p. 425 - 434 (2015/11/27)
The cDNAs for morphine 6-dehydrogenase (AKR1C34) and its homologous aldo-keto reductase (AKR1C35) were cloned from golden hamster liver, and their enzymatic properties and tissue distribution were compared. AKR1C34 and AKR1C35 similarly oxidized various xenobiotic alicyclic alcohols using NAD+, but differed in their substrate specificity for hydroxysteroids and inhibitor sensitivity. While AKR1C34 showed 3α/17β/20α-hydroxysteroid dehydrogenase activities, AKR1C35 efficiently oxidized various 3β- and 17β-hydroxysteroids, including biologically active 3β-hydroxy-5α/β-dihydro-C19/C21-steroids, dehydroepiandrosterone and 17β-estradiol. AKR1C35 also differed from AKR1C34 in its high sensitivity to flavonoids, which inhibited competitively with respect to 17β-estradiol (Ki 0.11-0.69 μM). The mRNA for AKR1C35 was expressed liver-specific in male hamsters and ubiquitously in female hamsters, whereas the expression of the mRNA for AKR1C34 displayed opposite sexual dimorphism. Because AKR1C35 is the first 3(17)β-hydroxysteroid dehydrogenase in the AKR superfamily, we also investigated the molecular determinants for the 3β-hydroxysteroid dehydrogenase activity by replacement of Val54 and Cys310 in AKR1C35 with the corresponding residues in AKR1C34, Ala and Phe, respectively. The mutation of Val54Ala, but not Cys310Phe, significantly impaired this activity, suggesting that Val54 plays a critical role in recognition of the steroidal substrate.
Rabbit 3-hydroxyhexobarbital dehydrogenase is a NADPH-preferring reductase with broad substrate specificity for ketosteroids, prostaglandin D2, and other endogenous and xenobiotic carbonyl compounds
Endo, Satoshi,Matsunaga, Toshiyuki,Matsumoto, Atsuko,Arai, Yuki,Ohno, Satoshi,El-Kabbani, Ossama,Tajima, Kazuo,Bunai, Yasuo,Yamano, Shigeru,Hara, Akira,Kitade, Yukio
, p. 1366 - 1375 (2013/11/19)
3-Hydroxyhexobarbital dehydrogenase (3HBD) catalyzes NAD(P) +-linked oxidation of 3-hydroxyhexobarbital into 3-oxohexobarbital. The enzyme has been thought to act as a dehydrogenase for xenobiotic alcohols and some hydroxysteroids, but its physiological function remains unknown. We have purified rabbit 3HBD, isolated its cDNA, and examined its specificity for coenzymes and substrates, reaction directionality and tissue distribution. 3HBD is a member (AKR1C29) of the aldo-keto reductase (AKR) superfamily, and exhibited high preference for NADP(H) over NAD(H) at a physiological pH of 7.4. In the NADPH-linked reduction, 3HBD showed broad substrate specificity for a variety of quinones, ketones and aldehydes, including 3-, 17- and 20-ketosteroids and prostaglandin D2, which were converted to 3α-, 17β- and 20α-hydroxysteroids and 9α,11β- prostaglandin F2, respectively. Especially, α-diketones (such as isatin and diacetyl) and lipid peroxidation-derived aldehydes (such as 4-oxo- and 4-hydroxy-2-nonenals) were excellent substrates showing low Km values (0.1-5.9 μM). In 3HBD-overexpressed cells, 3-oxohexobarbital and 5β-androstan-3α-ol-17-one were metabolized into 3-hydroxyhexobarbital and 5β-androstane-3α,17β-diol, respectively, but the reverse reactions did not proceed. The overexpression of the enzyme in the cells decreased the cytotoxicity of 4-oxo-2-nonenal. The mRNA for 3HBD was ubiquitously expressed in rabbit tissues. The results suggest that 3HBD is an NADPH-preferring reductase, and plays roles in the metabolisms of steroids, prostaglandin D2, carbohydrates and xenobiotics, as well as a defense system, protecting against reactive carbonyl compounds.
Novel steroid inhibitors of glucose 6-phosphate dehydrogenase
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)
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.
