22847-91-2Relevant articles and documents
Letter: A stereospecific total synthesis of racemic 11alpha-hydroxyprogesterone via a biomimetic polyene cyclization.
Johnson,Escher,Metcalf
, p. 1039 - 1034 (1976)
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Reichstein,Fuchs
, p. 684,686 (1940)
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Mancera et al.
, p. 1066,1068 (1952)
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Microbial hydroxylation of some steroids by Aspergillus wentii MRC 200316
Yildirim, Kudret
, p. 1273 - 1281 (2010)
Biotransformations of epiandrosterone (1), dehydroepiandrosterone (2) and pregnenolone (3) by Aspergillus wentii MRC 200316 for 5 days have been reported. Incubation of epiandrosterone (1) afforded 11α-hydroxy-5α- androstane-3,17-dione (4) and 3β,11α-dihydroxy-5α-androstan-17- one (5). Incubation of dehydroepiandrosterone (2) afforded 3β,7β- dihydroxyandrost-5-en-17-one (6) and 3β,7α-dihydroxyandrost-5-en-17- one (7). Incubation of pregnenolone (3) afforded only 11α-hydroxypregn-4- ene-3,20-dione (8).
Biotransformation of progesterone by the ascomycete Aspergillus niger N402
Savinova,Solyev,Vasina,Tyazhelova,Fedorova,Savinova
, p. 26 - 31 (2018)
The ability of the ascomyceteAspergillus niger N402 to transform exogenous progesterone was investigated. We found that this strain has steroid-hydroxylating activity and can introduce a hydroxyl group into the progesterone molecule mainly at positions C11(α) and C21 with predominant formation of 21-hydroxyprogesterone (deoxycortone). In addition, formation of 6β,11α-dihydroxyprogesterone was also observed. Studying the effects of the growth medium composition and temperature on progesterone conversion by A. niger N402 showed that the most intense accumulation of 21-hydroxyprogesterone occurred in minimal synthetic medium at 28°C. Increasing the cultivation temperature to 37°C resulted in almost complete inhibition of the hydroxylase activity in the minimal medium. In the complete medium, a similar increase in temperature inhibited 11α-hydroxylase activity and completely suppressed 6β-hydroxylase activity, but it produced no effect on 21-hydroxylating activity.
Dehalogenation methodof 9-halogenated steroid compound and application
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Paragraph 0197-0199, (2021/01/11)
The invention provides a dehalogenation method of a 9-halogenated steroid compound and application, and relates to the technical field of chemical synthesis. The dehalogenation method of the 9-halogenated steroid compound comprises the following steps: reacting a compound I with a hydrogen donor and an azo radical initiator to obtain a 9-dehalogenated product compound II of the 9-halogenated steroid compound. According to the dehalogenation method of the 9-halogenated steroid compound, a hydrogen donor adopts one or a combination of more of hypophosphorous acid and hypophosphite, formic acid and formate, organic silicon hydride, hydrazine compounds or cyclohexene, and an initiator adopts an azo free radical initiator. Reagents such as chromium, divalent chromium salt, trivalent chromium salt or tributyltin hydride which are high in toxicity and cause serious pollution to the environment are not used in the reaction, the method is green and environmentally friendly, the synthesis process is simple, convenient and easy to implement, and the production applicability is improved.
Engineering of CYP106A2 for steroid 9α- and 6β-hydroxylation
Nikolaus, Julia,Nguyen, Kim Thoa,Virus, Cornelia,Riehm, Jan L.,Hutter, Michael,Bernhardt, Rita
, p. 41 - 48 (2017/03/17)
CYP 106A2 from Bacillus megaterium ATCC 13368 has been described as a 15β-hydroxylase showing also minor 11α-, 9α- and 6β-hydroxylase activity for progesterone conversion. Previously, mutant proteins with a changed selectivity towards 11α-OH-progesterone have already been produced. The challenge of this work was to create mutant proteins with a higher regioselectivity towards hydroxylation at positions 9 and 6 of the steroid molecule. 9α-hydroxyprogesterone exhibits pharmaceutical importance, because it is a useful intermediate in the production of physiologically active substances which possess progestational activity. Sixteen mutant proteins were selected from a library containing mutated proteins created by a combination of site-directed and saturation mutagenesis of active site residues. Four mutant proteins out of these catalyzed the conversion of progesterone to 9α-OH-progesterone as a main product. For further optimization site-directed mutagenesis was performed. The introduction of seven mutations (D217V, A243V, A106T, F165L, T89N, T247V or T247W) into these four mutant proteins led to 28 new variants, which were also used for an in vivo conversion of progesterone. The best mutant protein, F165L/A395E/G397V, showed a ten-fold increase in the selectivity towards progesterone 9α-hydroxylation compared with the wild type CYP106A2. Also 6β-OH-progesterone is a pharmaceutically important compound, especially as intermediate for the production of drugs against breast cancer. For the rational design of mutant proteins with 6β-selectivity, docking of the 3D-structure of CYP106A2 with progesterone was performed. The introduction of three mutations (T247A, A243S, F173A) led to seven new mutant proteins. Clone A243S showed the greatest improvement in 6β-selectivity being more than ten-fold. Finally, an in vivo conversion of 11-deoxycorticosterone (DOC), testosterone and cortisol with the best five mutant proteins displaying 9α- or 6β-hydroxylation, respectively, of progesterone was performed to investigate whether the introduced mutations also effected the conversion of other substrates.
