- Biotransformation of 5-en-3β-ol steroids by Mucor circinelloides lusitanicus
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In this work, we report the mode of biotransformation of 5-en-3β-ol steroids using Mucor circinelloides lusitanicus for the first time. Here, we selected seven 5-en-3β-ol steroids as substrates. The main characteristic of the fungus was to introduce a 7α-hydroxyl group into substrates 1--5. With substrate 2, 3β, 7α, 11α-trihydroxypregna-5-en-20-one (2b) was obtained as the final product in good yield (46.4%). All the metabolites were determined by infrared spectra, high-resolution mass spectrometry, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance.
- Shan, Lihong,Jiao, Kai,Yin, Minghui,Huang, Jiajia,Chen, Yanjie,Qin, Shangshang,Liu, Hongmin
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Read Online
- Steroid hydroxylations with Botryodiplodia malorum and Colletotrichum lini
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An improved procedure for the microbial hydroxylations of dehydroepiandrosterone (DHEA, 1) and 15β,16β-methylene-dehydroepiandrosterone (2) was studied using whole cells of Botryodiplodia malorum and Colletotrichum lini. C. lini catalyzed 7α- and 15α-hydroxylation of 1 and 7α-hydroxylation of 2, while B. malorum gave 7β-hydroxylation of both the substrates. The stability of the enzymatic activity was higher in the presence of co-substrates (i.e., glucose or mannitol) allowing for repeated batches of the biotransformations. The yields of 7α,15α-dihydroxy-1 production were improved obtaining 5.8 g l-1 (recovered product) from 7.0 g l-1 of substrate. The structures of the hydroxylated products were assigned by a combination of two-dimensional NMR proton-proton and proton-carbon correlation techniques.
- Romano, Andrea,Romano, Diego,Ragg, Enzio,Costantino, Francesca,Lenna, Roberto,Gandolfi, Raffaella,Molinari, Francesco
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- Anti-proliferative action of endogenous dehydroepiandrosterone metabolites on human cancer cell lines.
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Dehydroepiandrosterone (DHEA) is a naturally occurring steroid synthesized in the adrenal cortex, gonads, brain, and gastrointestinal tract, and it is known to have chemopreventive and anti-proliferative actions on tumors. These effects are considered to be induced by the inhibition of glucose-6-phosphate dehydrogenase (G6PD) and/or HMG-CoA reductase (HMGR) activities. The present study was undertaken to investigate whether endogenous DHEA metabolites, i.e. DHEA-sulfate, 7-oxygenated DHEA derivatives, androsterone, epiandrosterone, and etiocholanolone, have anti-proliferative effects on cancer cells and to clarify which enzyme, G6PD or HMGR, is responsible for growth inhibition. Growth of Hep G2, Caco-2, and HT-29 cells, evaluated by 3-[4,5-dimethylthiazol]-2yl-2,5-diphenyl tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays, was time- and dose-dependently inhibited by addition of all DHEA-related steroids we tested. In particular, the growth inhibition due to etiocholanolone was considerably greater than that caused by DHEA in all cell lines. The suppression of growth of the incubated steroids was not correlated with the inhibition of G6PD (r=-0.031, n=9, NS) or HMGR (r=0.219, n=9, NS) activities. The addition of deoxyribonucleosides or mevalonolactone to the medium did not overcome the inhibition of growth induced by DHEA or etiocholanolone, while growth suppression by DHEA was partially prevented by the addition of ribonucleosides. These results demonstrate that endogenous DHEA metabolites also have an anti-proliferative action that is not induced by inhibiting G6PD or HMGR activity alone. These non-androgenic DHEA metabolites may serve as chemopreventive or anti-proliferative therapies.
- Yoshida, Shigemasa,Honda, Akira,Matsuzaki, Yasushi,Fukushima, Sugano,Tanaka, Naomi,Takagiwa, Aya,Fujimoto, Yoshinori,Miyazaki, Hiroshi,Salen, Gerald
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- Enhancement of steroid hydroxylation yield from dehydroepiandrosterone by cyclodextrin complexation technique
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The cyclodextrins (CDs) complexation technique was performed for the enhancement of hydroxylation yield from dehydroepiandrosterone (DHEA) by Colletotrichum lini ST-1. Using DHEA/methyl-β-cyclodextrin (M-β-CD) or DHEA/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes as substrate (10 g/L), the hydroxylation yields were increased by 14.98% and 20.54% respectively, and the biotransformation course was shortened by 12 h. X-ray diffractometry, differential scanning calorimetry, and phase solubility analyses showed an inclusion complex was formed between CDs and DHEA at a molar ratio of 1:1, which remarkably increased the solubility of DHEA, and then improved substrate biotransformation efficiency and hydroxylation yield. Meanwhile, results of thermodynamic parameters (ΔG, ΔH, ΔS and Ks) analysis revealed the complexation process was spontaneous and DHEA/CDs inclusion complex was stable. Scanning electron microscopy and transmission electron microscopy showed that the enhancement of DHEA hydroxylation yield also depended on the improvement of cell permeability through interaction between cytomembrane and CDs. These results suggested that the CDs complexation technique was a promising method to enhance steroids hydroxylation yield by increasing steroids solubility and decreasing membrane resistance of substrate and product during biotransformation process.
- Wu, Yan,Li, Hui,Lu, Zhen-Ming,Li, Heng,Rao, Zhi-Ming,Geng, Yan,Shi, Jin-Song,Xu, Zheng-Hong
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- Microbial transformation of dehydroepiandrosterone (DHEA) by some fungi
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In this work, biotransformations of dehydroepiandrosterone (DHEA) 1 by Ulocladium chartarum MRC 72584, Cladosporium sphaerospermum MRC 70266 and Cladosporium cladosporioides MRC 70282 have been reported. U. chartarum MRC 72584 mainly hydroxylated 1 at C-7α and C-7β, accompanied by a minor hydroxylation at C-4β, a minor epoxidation from the β-face and a minor oxidation at C-7 subsequent to its hydroxylations. 3β,7β-Dihydroxy-5β,6β-epoxyandrostan-17-one 6, 3β,4β,7α-trihydroxyandrost-5-en-17-one 7 and 3β,4β,7β-trihydroxyandrost-5-en-17-one 8 from this incubation were identified as new metabolites. C. sphaerospermum MRC 70266 converted some of 1 into a 3-keto-4-ene steroid and then hydroxylated at C-6α, C-6β and C-7α, accompanied a minor 5α-reduction and a minor oxidation at C-6 following its hydroxylations. C. sphaerospermum MRC 70266 also hydroxylated some of 1 at C-7α and C-7β. C. cladosporioides MRC 70282 converted almost half of 1 into a 3-keto-4-ene steroid and then hydroxylated at C-6α and C-6β. C. cladosporioides MRC 70282 also reduced some of 1 at C-17.
- Yildirim, Kudret,Kuru, Ali,Y?lmazer Keskin, Semra,Ergin, Sinan
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p. 465 - 474
(2020/11/12)
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- Oxidative Diversification of Steroids by Nature-Inspired Scanning Glycine Mutagenesis of P450BM3 (CYP102A1)
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Steroidal compounds are some of the most prescribed medicines, being indicated for the treatment of a variety of conditions including inflammation, heart disease, and cancer. Synthetic approaches to functionalized steroids are important for generating steroidal agents for drug screening and development. However, chemical activation is challenging because of the predominance of inert, aliphatic C-H bonds in steroids. Here, we report the engineering of the stable, highly active bacterial cytochrome P450 enzyme P450BM3 (CYP102A1) from Bacillus megaterium for the mono- and dihydroxylation of androstenedione (AD), dehydroepiandrosterone (DHEA), and testosterone (TST). In order to design altered steroid binding orientations, we compared the structure of wild type P450BM3 with the steroid C19-demethylase CYP19A1 with AD bound within its active site and identified regions of the I helix and the β4 strand that blocked this binding orientation in P450BM3. Scanning glycine mutagenesis across 11 residues in these two regions led to steroid oxidation products not previously reported for P450BM3. Combining these glycine mutations in a second round of mutagenesis led to a small library of P450BM3 variants capable of selective (up to 97%) oxidation of AD, DHEA, and TST at the widest range of positions (C1, C2, C6, C7, C15, and C16) by a bacterial P450 enzyme. Computational docking of these steroids into molecular dynamics simulated structures of selective P450BM3 variants suggested crucial roles of glycine mutations in enabling different binding orientations from the wild type, including one that closely resembled that of AD in CYP19A1, while other mutations fine-tuned the product selectivity. This approach of designing mutations by taking inspiration from nature can be applied to other substrates and enzymes for the synthesis of natural products and their derivatives.
- Cao, Yang,Chen, Wenyu,Fisher, Matthew J.,Leung, Aaron,Wong, Luet L.
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p. 8334 - 8343
(2020/09/18)
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- 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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- Hydroxylation of DHEA and its analogues by Absidia coerulea AM93. Can an inducible microbial hydroxylase catalyze 7α- and 7β-hydroxylation of 5-ene and 5α-dihydro C19-steroids?
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In this paper we focus on the course of 7-hydroxylation of DHEA, androstenediol, epiandrosterone, and 5α-androstan-3,17-dione by Absidia coerulea AM93. Apart from that, we present a tentative analysis of the hydroxylation of steroids in A. coerulea AM93. DHEA and androstenediol were transformed to the mixture of allyl 7-hydroxy derivatives, while EpiA and 5α-androstan-3,17-dione were converted mainly to 7α- and 7β-alcohols accompanied by 9α- and 11α-hydroxy derivatives. On the basis of (i) time course analysis of hydroxylation of the abovementioned substrates, (ii) biotransformation with resting cells at different pH, (iii) enzyme inhibition analysis together with (iv) geometrical relationship between the C-H bond of the substrate undergoing hydroxylation and the cofactor-bound activated oxygen atom, it is postulated that the same enzyme can catalyze the oxidation of C7-Hα as well as C7-H β bonds in 5-ene and 5α-dihydro C19-steroids. Correlations observed between the structure of the substrate and the regioselectivity of hydroxylation suggest that 7β-hydroxylation may occur in the normal binding enzyme-substrate complex, while 7α-hydroxylation - in the reverse inverted binding complex.
- Milecka-Tronina, Natalia,Ko?ek, Teresa,?wizdor, Alina,Panek, Anna
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p. 883 - 891
(2014/01/23)
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- Potential of Azadirachta indica cell suspension culture to produce biologically active metabolites of dehydroepiandrosterone
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Dehydroepiandrosterone (1) was investigated for biotransformation studies using the plant cell suspension culture of Azadirachta indica A. Juss. for the first time, yielding metabolites 2-6: 5α,3,17-androstanedione (2), 5-androstene-3β,17β-diol (3), 3β-hydroxyandrostan-17-one (4), 3β,11α-dihydroxy-5-androsten-17-one (5), and 3β,7α- dihydroxy-5-androsten-17-one (6), whose structures were solved through modern spectroscopic methods. All five compounds 2-6 have not been reported obtained by this way before. This is a new method to biosynthesize compounds 2-6 employing cultured cells of A. indica. Metabolites 2, 3, and 6 are important biologically active compounds, whereas 4 is a precursor for the production of the 7-hydroxylated compound having antiglucocorticoid and neuroprotective effects.
- Saifullah,Khan, Saifullah,Azizuddin,Choudhary, Muhammad Iqbal
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p. 671 - 676
(2013/11/06)
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- Biotransformation of some steroids by Mucor hiemalis MRC 70325
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In this work, incubations of testosterone, dehydroepiandrosterone and pregnenolone with Mucor hiemalis MRC 70325 have been reported. Incubation of testosterone afforded androst-4-en-3,17-dione (3%), 14a-hydroxyandrost- 4-en-3,17-dione (9%), 6β-hydroxyandrost-4-en-3,17-dione (2%) and 14a,17β-dihydroxyandrost-4-en-3-one (62%). Incubation of dehy droepiandrosterone afforded 3β,17β-dihydroxyandrost-5-ene (6%) and 3β,7α-dihydroxyandrost-5- en-17-one (72%). Incubation of pregnenolone afforded 3β,14a-dihydroxypregn-5-en-7,20-dione (3%), 3β,7α- dihydroxypregn- 5-en-20-one (64%) and 3β,7α,11α- trihydroxypregn-5-en-20-one (11%). 3β,14a-Dihydroxypregn-5-en-7,20-dione was identified as a new metabolite. Website
- Yildirim, Kudret,Saran, Hilal,Dolu, Omer Faruk,Kuru, Ali
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p. 566 - 569
(2013/10/22)
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- Biotransformation of 3β-hydroxy-5-en-steroids by Mucor silvaticus
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The biotransformation of four 3β-hydroxy-5-en-steroids with varying substituents at C-16 or/and C-17 by Mucor silvaticus was investigated. The characterization of the metabolites was performed by IR, MS, 1H NMR, 13C NMR, and 2-D NMR.
- Wang, Yanjie,Sun, Dongmei,Chen, Zhibao,Ruan, Hongsheng,Ge, Wenzhong
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p. 168 - 174
(2013/09/12)
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- Baeyer-villiger oxidation of some steroids by Aspergillus tamarii MRC 72400
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Biotransformations of epiandrosterone (1), dehydroepiandrosterone (2), testosterone (3), progesterone (4) and pregnenolone (5) by Aspergillus tamarii MRC 72400 for 5 days have been reported and the results of these incubations have been compared with previously published data obtained with Aspergillus tamarii QM 1223. A. tamarii MRC 72400 showed higher Bayer-Villiger monooxygenase activities than A. tamarii QM 1223 did. Apart from pregnenolone (5), A. tamarii MRC 72400 metabolized these steroids in different ways. Incubation of epiandrosterone (1) afforded 3β,11β-dihydroxy-5α-androstan-17- one (6) (3%) and 3β-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (7) (9.5%). Incubation of dehydroepiandrosterone (2) afforded 3β-hydroxy-17a- oxa-D-homoandrost-5-en-17-one (8) (28%), testolactone (9) (6%), 3β,7β-dihydroxyandrost-5-en-17-one (10) (13%) and 3β,7α- dihydroxyandrost- 5-en-17-one (11) (24%). Incubation of testosterone (3) afforded testolactone (9) (58%). Incubation of progesterone (4) also afforded testolactone (9), however in higher yield (86%). Incubation of pregnenolone (5) afforded 3β-hydroxy-17a-oxa-D-homoandrost- 5-en-17-one (8) (25%) and testolactone (9) (27%).
- Yildirim, Kudret,Uzuner, Ahmet,Gulcuoglu, Emine Yasemin
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experimental part
p. 743 - 754
(2011/12/03)
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- Hydroxylation of DHEA, androstenediol and epiandrosterone by Mortierella isabellina AM212. Evidence indicating that both constitutive and inducible hydroxylases catalyze 7α- as well as 7β-hydroxylations of 5-ene substrates
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The course of transformation of DHEA, androstenediol and epiandrosterone in Mortierella isabellina AM212 culture was investigated. The mentioned substrates underwent effective hydroxylation; 5-ene substrates - DHEA and androstenediol - were transformed into a mixture of 7α- and 7β- allyl alcohols, while epiandrosterone was converted into 7α- (mainly), 11α- and 9α- monohydroxy derivatives. Ketoconazole and cycloheximide inhibition studies suggest the presence of constitutive and substrate-induced hydroxylases in M. isabellina. On the basis of time course analysis of the hydroxylation of DHEA and androstenediol, the oxidation of allyl C7-Hα and C7-Hβ bonds by the same enzyme is a reasonable assumption.
- Kolek, Teresa,Milecka, Natalia,Swizdor, Alina,Panek, Anna,Bialonska, Agata
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experimental part
p. 5414 - 5422
(2011/09/13)
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- Synthesis of dehydroepiandrosterone analogues modified with phosphatidic acid moiety
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Dehydroepiandrosterone (DHEA) and its metabolite 7α-OH DHEA have many diverse physiological, biological and biochemical effects encompassing various cell types, tissues and organs. In in vitro studies, DHEA analogues have myriad biological actions, but in vivo, especially in oral administration, DHEA produces far more limited clinical effects. One of the possible solutions of this problem is conversion of DHEA to active analogues and/or its transformation into prodrug form. In this article, the studies on the conversion of DHEA and 7α-OH DHEA into their phosphatides by the phosphodiester approach are described. In this esterification, N,N-dicyclohexylcarbodiimide (DCC) was the most efficient coupling agent as well as p-toluenesulphonyl chloride (TsCl).
- Smuga, Damian A.,Smuga, Ma?gorzata,?wizdor, Alina,Panek, Anna,Wawrzeńczyk, Czes?aw
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experimental part
p. 1146 - 1152
(2010/11/03)
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- Microbial hydroxylation of some steroids by Aspergillus wentii MRC 200316
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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).
- Yildirim, Kudret
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experimental part
p. 1273 - 1281
(2011/09/20)
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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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- Biotransformations of steroid compounds by Chaetomium sp. KCH 6651
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Biotransformations of steroid compounds: androstenedione, testosterone, progesterone, pregnenolone and DHEA using Chaetomium sp. 1 KCH 6651 strain as a biocatalyst were investigated. The microorganism proved capable of selective hydroxylation of the steroid substrates. Androstenedione was converted to 14α-hydroxyandrost-4-en-3,17-dione (in over 75% yield) and 6β-hydroxyandrost-4-en-3,17-dione (in low yield), while testosterone underwent regioselective hydroxylation at 6β position. Progesterone was transformed to a single product-6β,14α-dihydroxypregnan-4-en-3,20-dione in high yield, whereas biotransformation of DHEA resulted in the formation of 7α-hydroxy derivative, which was subsequently converted to 7α-hydroxyandrost-4-en-3,17-dione.
- Janeczko, Tomasz,Dmochowska-Gladysz, Jadwiga,Kostrzewa-Suslow, Edyta,Bialonska, Agata,Ciunik, Zbigniew
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experimental part
p. 657 - 661
(2009/07/19)
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- METHODS FOR PREPARING 17-ALKYNYL-7-HYDROXY STEROIDS AND RELATED COMPOUNDS
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The invention relates to processes for preparing 17-alkynyl-7-hydroxy- steroids, such as 17-Ethynyl-10R13S-dimethyl 2,3,4,7,8R,9S, 10,11,12,13,14S,15,16,17-hexadecahydro-1 H-cyclopenta[a]phenanthrene- 3R,7R,17S-triol (also referred to as 17α-ethynyl-androst-5-ene-3β,7β,17β-triol), that are essentially free of process impurities having binding activity at nuclear estrogen receptors.
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Page/Page column 19
(2009/12/28)
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- Synthesis of 3β-hydroxy-androsta-5,7-dien-17-one from 3β-hydroxyandrost-5-en-17-one via microbial 7α-hydroxylation
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The synthesis of 3β-hydroxy-androsta-5,7-dien-17-one from 3β-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA) via microbial 7α-hydroxylation has been accomplished. At the first stage, 3β,7α-dihydroxy-androst-5-en-17-one was obtained in high yiel
- Lobastova, Tatyana G.,Khomutov, Sergey M.,Vasiljeva, Ljudmila L.,Lapitskaya, Margarita A.,Pivnitsky, Kasimir K.,Donova, Marina V.
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experimental part
p. 233 - 237
(2009/04/14)
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- A chemobiological synthesis of eplerenone
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This paper will describe an approach to the synthesis of eplerenone, which is being marketed for the treatment of hypertension. The synthesis begins with DHEA available from wild yams and uses a combination of microbiological and chemical transformations to build eplerenone. Georg Thieme Verlag Stuttgart.
- Wuts, Peter G. M.,Anderson, Andrew M.,Ashford, Scott W.,Goble, Michael P.,White, Michael J.,Beck, Doris,Gilbert, Ivan,Hrab
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p. 418 - 422
(2008/09/17)
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- Novel methods for the preparation of dhea derivatives
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The invention relates to a method for the production of DHEA derivatives, such as 7-oxo-DHEA and 7-hydroxy-DHEA, from DHEA itself.
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Page/Page column 10-11
(2010/11/25)
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- MICROBIAL PROCESS FOR THE PREPARATION OF 7-KETO DEHYDROEPIANDROSTERONE AND RELATED ANALOGS
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The present invention relates to a two part microbial process for the preparation of 7-oxo-5-androstene steroids of Formula III.
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- Synthesis of 7α-hydroxy-dehydroepiandrosterone and 7β-hydroxy-dehydroepiandrosterone
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The fermentation of dehydroepiandrosterone synthesized from the starting material diosgenin using Mucor racemosus produced 7α-hydroxy- dehydroepiandrosterone and 7β-hydroxy-dehydroepiandrosterone. The bioactivity of the microbial metabolites is also discussed. The species M. racemosus was isolated by screening among stains from soil samples collected from various parts of China.
- Li, Heping,Liu, Hong-Min,Ge, Wenzhong,Huang, Lihua,Shan, Lihong
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p. 970 - 973
(2007/10/03)
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- Derivatives of 16α-hydroxy-dehydroepiandrosterone with an additional 7-oxo or 7-hydroxy substituent: Synthesis and gas chromatography/mass spectrometry analysis
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Derivatives of 16α-hydroxy-dehydroepiandrosterone, which have an additional oxygen substituent at position 7 (oxo or hydroxy group), were synthesized. Firstly, 17,17-dimethoxyandrost-5-ene-3β,16α-diyl diacetate was prepared and then oxidized with a complex of chromium(VI) oxide and 2,5-dimethylpyrazole to the respective 7-oxo derivative. This key intermediate was both deprotected or reduced by l-Selectride or sodium borohydride in the presence of cerium(III) chloride and then deprotected to give 7-oxo, 7α-hydroxy and 7β-hydroxy derivatives of 16α-hydroxy-dehydroepiandrosterone. The target compounds were characterized by 1H and 13C NMR spectra and in the form of O-methyloxime-trimethylsilyl derivatives, by gas chromatography/mass spectrometry methods.
- Pouzar, Vladimír,?erny, Ivan,Hill, Martin,Bi?íková, Marie,Hampl, Richard
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p. 739 - 749
(2007/10/03)
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- New efficient and totally stereoselective copper allylic benzoyloxylation of sterol derivatives
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A new efficient and totally stereoselective copper allylic benzoyloxylation of sterol derivatives has been developed. This methodology has been successfully applied to the synthesis of 7α-hydroxy DHEA and 7α-hydroxy cholesterol in a two-step synthesis with high chemical yields (77% and 61% overall yield, respectively). A mechanistic rationale justifying the total stereoselectivity encountered has been proposed.
- Brunel, Jean Michel,Billottet, Ludovic,Letourneux, Yves
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p. 3036 - 3041
(2007/10/03)
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- 5-Androsten-3beta-ol steroid intermediates and processes for their preparation
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The present invention provides 5-androsten-3β-ol steroid intermediates and processes for their preparation.
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- Processes for preparing C-7 substituted steroids
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This invention relates to processes for the preparation of novel 7-carboxy substituted steroid compounds of Formula I,
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Page/Page column 8
(2008/06/13)
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- Microbial method for hydrolysis and oxidation of androst-5-ene and pregn-5-ene steroid esters
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A microbial method for hydrolysis and oxidation of androst-5-ene and pregn-5-ene steroid esters is disclosed.
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- Methods for preparing 7alpha-hydroxy-dehydroepiandrosterone
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The invention relates to new processes for preparing 7alpha-hydroxy-dehydroepiandrosterone of formula (1): 1
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- Purification of 7alpha-hydroxydehydroepiandrosterone and derivatives thereof and solvates obtained therefrom
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Novel solvates of 7α-hydroxydehydroepiandrosterone or derivatives thereof complexed with an alcohol are obtained by judiciously purifying a mixture of the 7α-OH and 7β-OH isomers.
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Page/Page column 3
(2008/06/13)
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- The microbiological hydroxylation of 3α,5-cycloandrostanes by Cephalosporium aphidicola
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The microbiological hydroxylation of some 3α,5-cycloandrostanes by the fungus, Cephalosporium aphidicola has been shown to take place at C-2α and C-14α and a 6β-alcohol was oxidized to the 6-ketone.
- Bensasson, Caroline S.,Hanson, James R.,Le Huerou, Yvan
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p. 1279 - 1282
(2007/10/03)
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- Steroid transformations with Fusarium oxysporum var. cubense and Colletotrichum musae
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The utility of two locally isolated fungi, pathogenic to banana, for steroid biotransformation has been studied. The deuteromycetes Fusarium oxysporum var. cubense (IMI 326069, UAMH 9013) and Colletotrichum musae (IMI 374528, UAMH 8929) had not been examined previously for this potential. In general, F. oxysporum var. cubense effected 7α hydroxylation on 3β-hydroxy- Δ5-steroids, 6β, 12β, and 15α hydroxylation on steroidal-4-ene-3-ones, side-chain degradation on 17α,21-dihydroxypregnene-3,20-diones, and 15α hydroxylation on estrone. Both strains were shown to perform redox reactions on alcohols and ketones.
- Wilson, Maureen R.,Gallimore, Winklet A.,Reese, Paul B.
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p. 834 - 843
(2007/10/03)
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- The hydroxylation of Δ5-androstenes by Cephalosporium aphidicola
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Whereas the major hydroxylation product of 3β-hydroxy-5α-androstan- 17-one by Cephalosporium aphidicola is the 11α-alcohol, the presence of a Δ5-double bond in the substrate leads to non-stereospecific allylic hydroxylation at C-7. Hydroxylation at C-11 became a minor transformation and there was no detectable hydroxylation at C-14.
- Bensasson, Caroline M.,Hanson, James R.,Hunter, A. Christy
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p. 2355 - 2358
(2007/10/03)
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- Ergosteroids II: Biologically active metabolites and synthetic derivatives of dehydroepiandrosterone
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An improved procedure for the synthesis of 3β-hydroxyandrost-5-ene- 7,17-dione, a natural metabolite of dehydroepiandrosterone (DHEA) is described. The synthesis and magnetic resonance spectra of several other related steroids are presented. Feeding dehydroepiandrosterone to rats induces enhanced formation of several liver enzymes among which are mitochondrial sn-glycerol 3-phosphate dehydrogenase (GPDH) and cytosolic malic enzyme. The induction of these two enzymes, that complete a thermogenic system in rat liver, was used as an assay to search for derivatives of DHEA that might be more active than the parent steroid. Activity is retained in steroids that are reduced to the corresponding 17β-hydroxy derivative, or hydroxylated at 7α or 7β, and is considerably enhanced when the 17-hydroxy or 17-carbonyl steroid is converted to the 7-oxo derivative. Several derivatives of DHEA did not induce the thermogenic enzymes whereas the corresponding 7-oxo compounds did. Both short and long chain acyl esters of DHEA and of 7-oxo-DHEA are active inducers of the liver enzymes when fed to rats. 7-Oxo-DHEA-3-sulfate is as active as 7-oxo-DHEA or its 3-acetyl ester, whereas DHEA-3-sulfate is much less active than DHEA. Among many steroids tested, those possessing a carbonyl group at position 3, a methyl group at 7, a hydroxyl group at positions 1, 2, 4, 11, or 19, or a saturated B ring, with or without a 4-5 double bond, were inactive.
- Lardy, Henry,Kneer, Nancy,Wei, Yong,Partridge, Bruce,Marwah, Padma
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p. 158 - 165
(2007/10/03)
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- Synthesis of (19E)-3β,7β-dihydroxy-17-oxoandrost-5-EN-19-AL 19-(O-carboxymethyl)oxime, new hapten for 7β-hydroxy-dehydroepiandrosterone (3β,7β-dihydroxyandrost-5-EN-17-one)
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(19E)-3β,7β-Dihydroxy-17-oxoandrost-5-en-19-al 19-(O-carboxymethyl)oxime (26) was prepared in 15 steps from 17-oxoandrost-5-en-3β-yl benzoate (2, DHEA benzoate). Protection of position 17 by a borohydride reduction and acetylation, subsequent functionalization of position 19 by hypoiodite reaction, oxidation to 19-aldehyde and oximation gave successively (19E)-19-oxoandrost-5-ene-3β,17β-diyl 17-acetate 3-benzoate 19-(O-carboxymethyl)oxime methyl ester (10). Then 7-keto group was introduced hy allylic oxidation with chromium(VI) oxide-3,5-dimethylpyrazole complex and stereoselectively reduced by borohydride in the presence of cerium(III) ions into 7β-hydroxy group. After protection as 7-isobutyrate the acetate at position 17 was removed and oxidation recovered 17-ketone. Final deprotection revealed both hydroxyl and carhoxyl groups, giving desired 19 CMO 7β-hydroxy DHEA designed as hupten for immunassays.
- Pouzar, Vladimir,Slavikova, Tereza,Cerny, Ivan
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p. 109 - 123
(2007/10/03)
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- Transformed steroids 195. Introduction of the 9α-hydroxygroup into Δ5-3β-hydroxysteroids by Circinella sp. mold
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A preparative method of 9α-hydroxylation of Δ5-3β-hydroxysteroids using the fungi of Circinella sp.IOKh-1220 not capable of modifying the ring A has been developed.It is established that the yields of the main and the side products greatly depend on the transformation conditions, mycelium age, and the structure of the steroid substrate.Under the optimal transformation conditions novel 9α-hydroxysubstituted derivatives of androstenolone, pregnenolone, 16-dehydro-16α,17α-epoxy-, and 16α-methoxypregnenolone have been obtained in 36-80percent yields. - Key words: hydroxylation, Δ5-3β-hydroxysteroids, Δ5-3β,9α-dihydroxysteroids, Circinella sp.
- Voishvillo, N. E.,Istomina, Z. I.,Kamernitsky, A. V.
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p. 689 - 695
(2007/10/02)
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- Microbiological Transformations. Part 3. The Oxidation of Androstene Derivatives with the Fungus Cunninghamella elegans
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The products obtained from the incubation of some Δ4- and Δ5-androstene derivatives with Cunninghamella elegans are largely those arising from allylic oxidation or epoxidation of the double bond, but some 9-, 12-, 14-, and 16-hydroxylation also occurs.
- Crabb, Trevor A.,Dawson, Philip J.,Williams, Roger O.
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p. 2535 - 2541
(2007/10/02)
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