- Immobilized heterologous Rhizopus Oryzae lipase as an efficient catalyst in the acetylation of cortexolone
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The enzymatic preparation of a monoacetyl derivative of the corticosteroid cortexolone, through a transesterification reaction, is described. The heterologous Rhizopus oryzae lipase, immobilized on three different supports, proved to be an efficient catalyst in the acylation reaction using a complex substrate such as cortexolone. Immobilization of the enzyme on Lewatit 1600 resin at pH = 7 and 25 °C was the best condition for catalysis of the acetylation reaction. The influence of various reaction parameters, such as the nature of the acetylating agent, the solvent, the temperature, and the ratios of acetylating agent to substrate, and enzyme to substrate, was evaluated. Using the response surface methodology and a central composite rotatable design, the specific yield of acetylated cortexolone was optimized by means of the study of the effect of the enzyme (E)/substrate (S) and the acylating agent (A)/substrate ratios. The ratios of 5 (E/S) and 31.6 (A/S) were predicted as the optimal values to reach the maximum specific yield of the product (P): 1.59 mmol P/mmol A·g E. The mild reaction conditions and low environmental impact make the biocatalytic procedure a convenient way to prepare the reported derivative of this biologically active steroid. The regioselective acetylation of cortexolone was achieved by using an immobilized heterologous Rhizopus oryzae lipase. The mild reaction conditions and low environmental impact make the biocatalytic procedure a convenient way to prepare the monoacetyl derivative of this biologically active steroid. Copyright
- Quintana, Paula G.,Guillen, Marina,Marciello, Marzia,Valero, Francisco,Palomo, Jose M.,Baldessari, Alicia
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- Method for treating prednisone acetate mother liquor
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The invention relates to the technical field of chemical pharmacy, in particular to a method for treating prednisone acetate mother liquor. The method comprises the following steps: (1) adding a solvent and alkali liquor into the prednisone acetate mother liquor to carry out hydrolysis reaction; (2) after the hydrolysis reaction is finished, adjusting the reaction liquid to be neutral, concentrating under reduced pressure until a large amount of crystals are separated out, and performing suction filtration to obtain a hydrolysate crude product; (3) adding the hydrolysate crude product into a solvent, and refining to obtain a hydrolyzed refined product; (4) adding the hydrolyzed refined substance and a catalyst into a solvent, and reacting with acetic anhydride to obtain a mixture of prednisone acetate and cortisone acetate; and (5) fermenting and dehydrogenating the mixture to obtain the prednisone acetate. According to the treatment method, the prednisone acetate in the prednisone acetate mother liquor can be recycled, particularly, the prednisone acetate in the mother liquor can be recycled, the treatment cost is saved, and the yield of the prednisone acetate is increased; The method can well remove the dehydrogenation RSA and RSA impurities, and is stable in processand simple to operate.
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Paragraph 0034-0066
(2021/06/02)
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- A by the 3,17-dione steroid preparing steroid the synthetic method of the compound of
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The invention discloses a synthetic method of steroid type drugs and intermediates, in particular relates to a synthetic method for preparing 17-hydroxy-20-ketone steroid compounds from 3,17-diketone steroids, and belongs to the field of synthesis of drugs. The method takes 3,17-diketone steroids as raw materials and adopts a conventional, environment-friendly, low-toxicity reagent, and the steroid type drugs such as cortisone, hydrocortisone, metacortandracin, or hydroprednisone, or intermediates 17alpha-hydroxy-20-ketone compounds are prepared simply and conveniently at high yield by selective protection of C3 or (and) C11-ketone group, Wittig reaction of C17, selective oxidization of 17(20)-position double bonds and halogenating replacement. The aftertreatment is simple, few three wastes are generated, the reaction selectivity is good, the yield is high, and byproducts anti-pregnancy steroidal drugs and steroidal compounds can be obtained. The raw materials are easy to get, the cost is low and the synthetic process is simple; the synthetic method is suitable for industrial production.
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- Potential corticoid metabolites: Chemical synthesis of 3- and 21-monosulfates and their double-conjugates of tetrahydrocorticosteroids in the 5 α- and 5 β-series
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Here, we describe the chemical synthesis of the complete sets of 18 novel 3- and 21-monosulfates and their double-conjugated form of tetrahydrocortisol (THF), tetrahydro-11-deoxycortisol (THS), and tetrahydrocortisone (THE) in the 5 α- and 5 β-series. The principal reactions involved are: (1) selective protection of a specific hydroxy group in substrates; (2) catalytic hydrogenation at C-5 of Δ4-3-ketosteroids with 10% Pd(OH) 2/C to yield 3-oxo-5 β-steroids and reductive allomerization with 10% Pd/C to yield 3-oxo-5 α-isomers; (3) reduction of the resulting 3-oxo-5 β- and 3-oxo-5 α-steroids to the corresponding 3 α-hydroxy-compounds with Zn(BH4)2 and K-Selectride, respectively; and (4) sulfation of hydroxy groups at C-3 and/or C-21 in the tetrahydrocorticosteroid derivatives with sulfur trioxide-triethylamine complex.
- Okihara, Rika,Mitamura, Kuniko,Hasegawa, Maki,Mori, Megumi,Muto, Akina,Kakiyama, Genta,Ogawa, Shoujiro,Iida, Takashi,Shimada, Miki,Mano, Nariyasu,Ikegawa, Shigeo
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experimental part
p. 344 - 353
(2011/02/22)
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- An efficient hemisynthesis of 20- and 21-[13C]-labeled cortexolone: A model for the study of skin sensitization to corticosteroids
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A method is described for the synthesis of isotopomers of cortexolone from the commercially available andros-4-ene-3, 17dione. The strategy is based on the use of K13CN for labeling at position 20 and of 13CH 3Mgl, generated in situ, for labeling at position 21. Because of the early introduction of the [13C] labeling, our efforts aimed at reproducible experimental procedures giving high yields with respect to the isotope containing precursors. During the development of this hemisynthesis, we noted that judicious choice of protective groups was essential as this could lead not only to mixtures or unstable intermediates but also influence considerably the output of reactions.
- Claudel, Emilie,Arbez-Gindre, Cecile,Berl, Valerie,Lepoittevin, Jean-Pierre
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scheme or table
p. 3391 - 3398
(2010/02/28)
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- Ruthenium-catalyzed Oppenauer-type oxidation of 3β-hydroxy steroids. A highly efficient entry into the steroidal hormones with 4-en-3-one functionality
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Oxidation of 5-unsaturated 3β-hydroxy steroids 1 to the corresponding 4-en-3-one derivatives 2 can be performed efficiently by acetone at reflux in the presence of a catalytic system consisting of either (PPh3)3RuCl2 (3) and K2CO3 or [(C4Ph4COHOCC4Ph4)(μ-H)][(CO)4Ru2] (4). The reaction proceeds via a ruthenium-catalyzed dehydrogenation of 1 and subsequent hydrogen transfer to acetone with concomitant double bond migration.
- Almeida, Maria L. S.,Kocǒvsky, Pavel,Báckvall, Jan-E?.
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p. 6587 - 6590
(2007/10/03)
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- Steroid intermediates and processes for their preparation
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Novel steroids having a 9α-hydroxy or a 9α-carbonate substituent can be prepared from 9α-hydroxyandrostenedione and can be utilized in the synthesis of commercially valuable corticosteroids such as betamethasone. The 9α-carbonates are prepared by reaction of the corresponding 9α-hydroxy steroid with a sequence of excess base, trialkylsilyl chloride, alkyl haloformate and alkanol or by using excess base, alkyl haloformate and alkoxide. 9α-Carbonate-17-keto compounds can be treated with lithium acetylide and a lithium salt to afford the corresponding 17α-ethynyl-17β-hydroxy-9α-carbonate. This compound is then esterified with a novel series of reagents to give the 17-ester which can be reduced the corresponding 17-allene. Oxidation of this allene to the bis-epoxide compound, followed by treatment with an alkali metal salt of a carboxylic acid under phase transfer conditions gives the 17α-hydroxy 21-ester 9α-carbonate. Elimination of the 9α-carbonate group affords the a 17α-hydroxy, 9(11)ene, which in a few subsequent steps can be converted to a variety of commercially important corticosteroids. Novel 9α-carbonate compounds are prepared in the various reaction steps.
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- Ruthenium-Catalyzed Oxidative Transformation of Alkenes to α-Ketols with Peracetic Acid. Simple Synthesis of Cortisone Acetate
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The reactions of alkenes with peracetic acid in the presence of RuCl3 catalyst gave the corresponding α-ketols, which are important building units for synthesis of biological active compounds, such as cortisone acetate.
- Murahashi, Shun-Ichi,Saito, Takao,Hanaoka, Hidenori,Murakami, Yoshihide,Naota, Takeshi,et al.
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p. 2929 - 2930
(2007/10/02)
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- 17 α-chloroethynyl pregnane derivatives
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Known pregnane derivatives are prepared by esterificiation of known androstane derivatives to give new ester of Formula III STR1 wherein in each case symbolizes a single bond or a double bond, n is 1 or 2, R1 is hydrogen or methyl, R2 is hydrogen or formyl, and R3 is chlorine, hydroxy or an alkanoyloxy group of up to 6 carbon atoms, and reaction of the latter with Ag(I) and formic acid.
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- Process and intermediates for the preparation of 17 alphahydroxyprogesterones and corticoids from an enol steroid
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This invention discloses an improved process for the production of corticoids from 17α-hydroxy steroids utilizing peroxymonosulfate.
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- FACILE SYNTHESIS OF CORTICOSTEROIDS FROM 17-KETOSTEROIDS VIA 20-CYANO-21-CARBOXYLATES
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Introduction of the dihydroxyacetone side chain at position 17 of steroidal skeleton via cyanocarbalkoxymethylidene derivatives is described.The latter compounds were obtained by condensation of corresponding 17-oxoandrostanes with ethyl cyanoacetate.Synthesis of 17α,21-dihydroxypregn-4-ene-3,20-dione 21-acetate (Reichstein's substance S acetate) is presented.Syntheses of model 17-deoxycorticosteroids from 17-cyanocarbalkoxymethylidene derivatives were carried out.
- Gumulka, Maria,Kurek, Alicja,Wicha, Jerzy
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p. 741 - 748
(2007/10/02)
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- Efficient Synthesis of the Corticosteroid Side-chain from 17-Ketones
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Steroidal 17-ketones react smoothly with diethyl α-isocyanoethyl phosphonate to give, after suitable oxidative and hydrolytic reactions, the dihydroxy-acetone side-chain of corticosteroids in high yield.
- Barton, Derek H. R.,Motherwell, William B.,Zard, Samir Z.
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p. 774 - 775
(2007/10/02)
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- Process for the preparation of 17α-hydroxyprogesterones and corticoids from androstenes
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This invention discloses a general process for the production of corticoids from androstenes. This invention provides an economically viable alternative synthesis of 17α-hydroxyprogesterones and the corticoids.
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