- The generation of a steroid library using filamentous fungi immobilized in calcium alginate Dedicated to the memory of Professor Sir John W. Cornforth, University of Sussex (1917-2013).
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Four fungi, namely, Rhizopus oryzae ATCC 11145, Mucor plumbeus ATCC 4740, Cunninghamella echinulata var. elegans ATCC 8688a, and Whetzelinia sclerotiorum ATCC 18687, were subjected to entrapment in calcium alginate, and the beads derived were used in the biotransformation of the steroids 3β,17β-dihydroxyandrost-5-ene (1) and 17β-hydroxyandrost-4-en-3-one (2). Incubations performed utilized beads from two different encapsulated fungi to explore their potential for the production of metabolites other than those derived from the individual fungi. The investigation showed that steroids from both single and crossover transformations were typically produced, some of which were hitherto unreported. The results indicated that this general technique can be exploited for the production of small libraries of compounds.
- Peart, Patrice C.,Reynolds, William F.,Reese, Paul B.
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- Biocatalyst mediated production of 6β,11α-dihydroxy derivatives of 4-ene-3-one steroids
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Biotransformation of steroids with 4-ene-3-one functionality such as progesterone (I), testosterone (II), 17α-methyltestosterone (III), 4-androstene-3,17-dione (IV) and 19-nortestosterone (V) were studied by using a fungal system belonging to the genera of Mucor (M881). The fungal system efficiently and quantitatively converted these steroids in regio- and stereo-selective manner into corresponding 6β,11α-dihydroxy compounds. Time course experiments suggested that the transformation was initiated by hydroxylation at 6β- or 11α-(10β-hydroxy in case of V) to form monohydroxy derivatives which upon prolonged incubation were converted into corresponding 6β,11α-dihydroxy derivatives. The fermentation studies carried out using 5 L table-top fermentor with substrates (I and II) clearly indicates that 6β,11α-dihydroxy derivatives of steroids with 4-ene-3-one functionality can be produced in large scale by using M881.
- Kolet, Swati P.,Niloferjahan, Siddiqui,Haldar, Saikat,Gonnade, Rajesh,Thulasiram, Hirekodathakallu V.
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p. 1152 - 1158
(2013/10/08)
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- Microbial Baeyer-Villiger oxidation of steroidal ketones using Beauveria bassiana: Presence of an 11α-hydroxyl group essential to generation of D-homo lactones
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This paper demonstrates for the first time transformation of a series of 17-oxo steroidal substrates (epiandrosterone, dehydroepiandrosterone, androstenedione) by the most frequently used whole cell biocatalyst, Beauveria bassiana, to 11α-hydroxy-17a-oxa-d-homo-androst-17-one products, in the following sequence of reactions: 11α-hydroxylation and subsequent Baeyer-Villiger oxidation to a ring-D lactone. 11α-Hydroxyprogesterone, the product of the first stage of the progesterone metabolism, was further converted along two routes: hydroxylation to 6β,11α- dihydroxyprogesterone or 17β-acetyl chain degradation leading to 11α-hydroxytestosterone, the main metabolite of the substrate. Part of 11α-hydroxytestosterone underwent a rare reduction to 11α-hydroxy- 5β-dihydrotestosterone. The experiments have demonstrated that the Baeyer-Villiger monooxygenase produced by the strain catalyzes solely oxidation of C-20 or C-17 ketones with 11α-hydroxyl group. 17-Oxo steroids, beside the 11α-hydroxylation and Baeyer-Villiger oxidation, also underwent reduction to 17β-alcohols; activity of 17β-hydroxysteroid dehydrogenase (17β-HSD) has significant impact on the amount of the formed ring-D δ-lactone.
- ?wizdor, Alina,Ko?ek, Teresa,Panek, Anna,Bia?on?ska, Agata
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experimental part
p. 253 - 262
(2012/03/10)
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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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- Microbial transformation of androst-4-ene-3,17-dione by Beauveria bassiana
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The microbial transformation of androst-4-ene-3,17-dione (I) by the fungus Beauveria bassiana CCTCC AF206001 has been investigated using pH 6.0 and 7.0 media. Two hydroxylated metabolites were obtained with the pH 6.0 medium. The major product was 11α-hydroxyandrost-4-ene-3,17-dione (II) whereas the minor product was 6β,11α-dihydroxyandrost-4-ene-3,17-dione (III). On the other hand, four hydroxylated and/or reduced metabolites were obtained with the pH 7.0 medium. The major product was 11α,17β-dihydroxyandrost-ene-3-one (V) and the minor products were 17β-hydroxyandrost-ene-3-one (IV), 6β,11α,17β-trihydroxyandrost-ene-3-one (VI) and 3α,11α,17β-trihydroxy-5α-androstane (VII). The products were purified by chromatographic methods, and were identified on the basis of spectroscopic methods. This fungus strain is clearly an efficient biocatalyst for 11α-hydroxylation and reduction of the 17-carbonyl group.
- Xiong, Zhigang,Wei, Qi,Chen, Hanmei,Chen, Shouwen,Xu, Wenjin,Qiu, Guofu,Liang, Shucai,Hu, Xianming
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p. 979 - 983
(2007/10/03)
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- Processes for preparation of 3-keto-7alpha-alkoxycarbonyl-delta-4,5- steroids and intermediates useful therein
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Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone and other compounds of Formula I wherein:-A-A- represents the group -CHR4-CHR5- or -CR4=CR5- R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, varyloxy;R1 represents an alpha-oriented lower alkoxycarbonyl or hydroxyalkyl radical;-B-B- represents the group -CHR6-CHR7- or an alpha- or beta- oriented group: where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy; andR8 and R9 are independently selected from the group consisting of hydrogen, hydroxy, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy, or R8 and R9 together comprise a carbocyclic or heterocyclic ring structure, or R8 or R9 together with R6 or R7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.
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- 5β-cyano-substituted steroid compounds
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Novel 5β-cyano steroid compounds including compounds of Formula VII: wherein A—A, B—B, R3, R8and R9are as defined in the specification.
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- Synthesis of 11-substituted androstenediones and testosterones as human decidual cell growth inhibitors
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11α-Hydroxytestosterone (1a), 11β-hydroxytestosterone (1b), 11α- methoxytestosterone (1c), 11β-methoxytestosterone (1d), 11-ketotestosterone (1e), and Δ(9(11))-testosterone (1f) were synthesized from hydrocortisone (4b) or 11-epi-hydrocortisone (4a). The six target compounds, together with 11α-methoxyandrostenedione (2c), 11β-methoxyandrostenedione, (2d) and their lead compound, testosterone (1), were found to effectively inhibit the growth and differentiation of human decidual cells in culture. There is no observable binding of these compounds to estrogen receptor of rabbit uterus. The introduction of a polar group (e.g., hydroxyl and carbonyl) to C-11 of androstenes decreases both the relative binding affinities to progesterone receptor and the inhibitory effects on human decidual cell growth, while the methylation of 11-hydroxyl group minimizes these effects. The similar effects of a polar group at C-11 of testosterone (1) on the inhibitory effects on human decidual cell growth and the relative binding affinities to progesterone receptor of rabbit uterus may suggest that one of the mechanisms of human decidual cell growth inhibition by these compounds is the anti- progestational activity of these androgens.
- Zhao, Qinjian,Li, Zhensu
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p. 190 - 195
(2007/10/02)
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- Radioimmunoassay agents
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Novel steroid derivatives containing a tyrosine ester amide group linked to an 11-hydroxysteroid alkylene dicarboxylic hemi-ester are described, suitable for iodination with radioactive iodine, useful in radioimmunoassay.
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