- Merging Halogen-Atom Transfer (XAT) and Cobalt Catalysis to Override E2-Selectivity in the Elimination of Alkyl Halides: A Mild Route towardcontra-Thermodynamic Olefins
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We report here a mechanistically distinct tactic to carry E2-type eliminations on alkyl halides. This strategy exploits the interplay of α-aminoalkyl radical-mediated halogen-atom transfer (XAT) with desaturative cobalt catalysis. The methodology is high-yielding, tolerates many functionalities, and was used to access industrially relevant materials. In contrast to thermal E2 eliminations where unsymmetrical substrates give regioisomeric mixtures, this approach enables, by fine-tuning of the electronic and steric properties of the cobalt catalyst, to obtain high olefin positional selectivity. This unprecedented mechanistic feature has allowed access tocontra-thermodynamic olefins, elusive by E2 eliminations.
- Zhao, Huaibo,McMillan, Alastair J.,Constantin, Timothée,Mykura, Rory C.,Juliá, Fabio,Leonori, Daniele
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supporting information
p. 14806 - 14813
(2021/09/18)
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- Preparation method of oxandrolone intermediate
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The invention belongs to the technical field of organic synthesis, and provides a preparation method of 17[beta]-hydroxy-17[alpha]-methyl-1-oxo-1,2-open-loop-A-nor-5[alpha]-androstane-2-oxygen-containing carboxylic acid. The preparation method comprises the following steps: 1) mixing mestanolone, 2-iodoxybenzoic acid, a catalyst and a solvent, and then carrying out an oxidation reaction to obtain a compound 1; and 2) mixing the compound 1, an aqueous solution of an oxidizing agent, bicarbonate and acetone, and then carrying out an oxidation reaction so as to obtain the 17[beta]-hydroxy-17[alpha]-methyl-1-oxo-1,2-open-loop-A-nor-5[alpha]-androstane-2-oxygen-containing carboxylic acid. The purity of the intermediate obtained by the preparation method is greater than or equal to 98%, and the yield is 95-97%; and the preparation method disclosed by the invention is low in required reaction temperature, short in product production period, simple to operate, low in production cost, friendly to environment, and reaction time is remarkably shortened.
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Paragraph 0039; 0040
(2021/07/01)
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- Characterization of desoxymethyltestosterone main urinary metabolite produced from cultures of human fresh hepatocytes
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Desoxymethyltestosterone (DMT; 17β-hydroxy-17α-methyl-5α- androst-2-ene) is a designer steroid present in hormonal supplements distributed illegally as such or in combination with other steroids, for self-administration. It figures on the list of substances prohibited in sports and its detection in athlete's urine samples is based upon the presence of the parent compound or the main urinary metabolite, which has not been characterized yet. Following its isolation from cultures of human fresh hepatocytes and S9 fractions of liver homogenates, we were able to identify this metabolite as being 17α-methyl-2β,3α,17β-trihydroxy-5α-androstane. Other minor metabolites were also characterized. The production, isolation, NMR, mass spectral analyses and chemical synthesis are presented.
- Gauthier, Julie,Poirier, Donald,Ayotte, Christiane
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experimental part
p. 635 - 643
(2012/06/01)
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- Development of a commercial process to produce oxandrolone
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A manufacturing scale process for the preparation of the anabolic steroid Oxandrolone was developed. Key elements included the following: the bromination of methylandrostanolone with perbromide to give the 2-bromoketone in ca. 80% yield with minimal dehydration, subsequent elimination of the bromide with Li2CO3/LiBr to give the 2-enone in ca. 70% yield with minimal formation of methyltestosterone, and an ozonolysis procedure to give the penultimate intermediate in ca. 90% yield. The overall yield from methylandrostanolone to Oxandrolone using the described process was 45% as compared to the original Searle yield of 8%.
- Cabaj, John E.,Kairys, David,Benson, Thomas R.
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p. 378 - 388
(2012/12/31)
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- Efficient oxidizing methods for the synthesis of oxandrolone intermediates
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Mild, efficient and eco-friendly oxidation of 17α-methylandrostan- 3β-17β-diol (1) has been studied with three different reagents viz. pentavalent iodine reagent 2-iodoxy benzoic acid (IBX) in DMSO at 65°C, sodium hypochlorite and H2O2/Na2WO4 under phase transfer conditions to give 17β-hydroxy-17α- methylandrostan-3-one (mestanolone 2), a drug intermediate as oxidized product. The H2O2/Na2WO4/PTC gave mestanolone in high yield and purity whereas sodium hypochlorite/PTC system yielded some chlorinated material along with the mestanolone. However, 1 with 2.5 equivalent of IBX gave 17β-hydroxy-17α-methyl- Δ1-androsten-3- one (3) under the similar reaction conditions in good yield and single step reaction.
- Ginotra, Sandeep K.,Chhikara, Bhupender S.,Singh, Manish,Chandra, Ramesh,Tandon, Vibha
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p. 989 - 991
(2007/10/03)
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- IBX in an ionic liquid: Eco-friendly oxidation of 17α- methylandrostan-3β,17β-diol, an intermediate in the synthesis of anabolic oxandrolone
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An easily available hypervalent iodine(V) reagent, 2-iodoxybenzoic acid (IBX) immobilized in the ionic liquid [bmim][Br] was found to be an efficient and eco-friendly protocol for the oxidation of 17α-methylandrostan- 3β,17β-diol (1). At ambient temperature oxidation of 1 with IBX gave mestanolone (2) in good yield and with an increased stoichiometric amount of IBX, oxidation adjacent to the carbonyl functionality (α,β- unsaturation) occurred to give dehydrogenated 17β-hydroxy-17α-methyl- Δ1-androsten-3-one (3) as the major product in a one-pot reaction. The product is easily obtained by extraction with diethyl ether and evaporation of the solvent.
- Chhikara, Bhupender S.,Chandra, Ramesh,Tandon, Vibha
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p. 7585 - 7588
(2007/10/03)
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- A convenient synthesis of oxandrolone through a regioselective Candida antarctica lipase-catalyzed transformation
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The use of a regioselective CAL-catalyzed transformation of a suitable intermediate allowed a convenient synthesis of oxandrolone, an anabolic hormone actually employed to improve the quality of life for patients with HIV-infections.
- Ferraboschi, Patrizia,Colombo, Diego,Prestileo, Paolo
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p. 2781 - 2785
(2007/10/03)
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- Process for the synthesis of oxandrolone
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A process is disclosed for synthesizing oxandrolone 1 involving the bromination of compound 2 to obtain compound 3, followed by the highly selective de-bromination of compound 3 to obtain compound 4, followed by the oxidation of compound 4 to obtain compound 6, and finally the reduction of compound 6 to obtain oxandrolone 1.
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- Process for the production of oxandrolone
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The present invention relates to a process for the synthesis of oxandrolone from mestanolone. The process comprises the steps of: (a) oxidizing mestanolone to form 17β-hydroxy-17α-methyl-5α-androst-1-en-3-one; (b) hydroxylating the 17β-hydroxy-17α-methyl-5α-androst-1-en-3-one to form 1α,2α,17β-trihydroxy-17α-methylandrostan-3-one; (c) cleaving the 1α,2α,17β-trihydroxy-17α-methylandrostan-3-one to form 17β-hydroxy-17α-methyl-1-oxo-1,2,-seco-A-nor-5α-androstan-2-oic acid; and (d) reducing the 17β-hydroxy-17α-methyl-1-oxo-1,2,-seco-A-nor-5α-androstan-2-oic acid to form oxandrolone.
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