Biological transformations of steroidal compounds: A review

Bhatti, Haq Nawaz; Khera, Rasheed Ahmad

doi:10.1016/j.steroids.2012.07.018

Cited by 148 publications

(72 citation statements)

References 101 publications

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“…Over the last years, biotechnological research in pharmacy has focused on the structural modification of bioactive steroids by using various microorganisms and their monooxygenases as transformation agents (whole‐cell biotransformations) 5, 6. Members of the cytochrome P450 monooxygenase superfamily (P450s), which catalyzes the transfer of oxygen from O 2 to a variety of organic compounds, are responsible for selective steroid oxyfunctionalizations 7.…”

Section: Introductionmentioning

confidence: 99%

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

et al. 2017

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Unspecific peroxygenases (UPO, EC 1.11.2.1) secreted by fungi open an efficient way to selectively oxyfunctionalize diverse organic substrates, including less‐activated hydrocarbons, by transferring peroxide‐borne oxygen. We investigated a cell‐free approach to incorporate epoxy and hydroxyl functionalities directly into the bulky molecule testosterone by a novel unspecific peroxygenase (UPO) that is produced by the ascomycetous fungus Chaetomium globosum in a complex medium rich in carbon and nitrogen. Purification by fast protein liquid chromatography revealed two enzyme fractions with the same molecular mass (36 kDa) and with specific activity of 4.4 to 12 U mg−1. Although the well‐known UPOs of Agrocybe aegerita (AaeUPO) and Marasmius rotula (MroUPO) failed to convert testosterone in a comparative study, the UPO of C. globosum (CglUPO) accepted testosterone as substrate and converted it with total turnover number (TTN) of up to 7000 into two oxygenated products: the 4,5‐epoxide of testosterone in β‐configuration and 16α‐hydroxytestosterone. The reaction performed on a 100 mg scale resulted in the formation of about 90 % of the epoxide and 10 % of the hydroxylation product, both of which could be isolated with purities above 96 %. Thus, CglUPO is a promising biocatalyst for the oxyfunctionalization of bulky steroids and it will be a useful tool for the synthesis of pharmaceutically relevant steroidal molecules.

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Section: Introductionmentioning

confidence: 99%

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

et al. 2017

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“…[6][7][8] This synthetic method can be used to prepare chemical structures that are difficult to obtain by ordinary chemical methods. The observed biotransformations may suggest metabolic pathways in mammals, due to similarity between mammalian and microbial systems.…”

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confidence: 99%

Chemical Synthesis of Uncommon Natural Bile Acids: The 9α-Hydroxy Derivatives of Chenodeoxycholic and Lithocholic Acids

Iida

Namegawa

Nakane

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The chemical synthesis of the 9α-hydroxy derivatives of chenodeoxycholic and lithocholic acids is reported. For initiating the synthesis of the 9α-hydroxy derivative of chenodeoxycholic acid, cholic acid was used; for the synthesis of the 9α-hydroxy derivative of lithocholic acid, deoxycholic acid was used. The principal reactions involved were (1) decarbonylation of conjugated 12-oxo-Δ 9(11) -derivatives using in situ generated monochloroalane (AlH 2 Cl) prepared from LiAlH 4 and AlCl 3 , (2) epoxidation of the deoxygenated Δ 9(11) -enes using m-chloroperbenzoic acid catalyzed by 4,4′-thiobis-(6-tert-butyl-3-methylphenol), (3) subsequent Markovnikov 9α-hydroxylation of the Δ 9(11) -enes with AlH 2 Cl, and (4) selective oxidation of the primary hydroxyl group at C-24 in the resulting 3α,9α,24-triol and 3α,7α,9α,24-tetrol to the corresponding C-24 carboxylic acids using sodium chlorite (NaClO 2 ) in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidine 1-oxyl free radical (TEMPO) and sodium hypochlorite (NaOCl). The 1 H-and 13 C-NMR spectra are reported. The 3α,7α,9α-trihydroxy-5β-cholan-24-oic acid has been reported to be present in the bile of the Asian bear, and its 7-deoxy derivative is likely to be a bacterial metabolite. These bile acids are now available as authentic reference standards, permitting their identification in vertebrate bile acids.

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“…The gradient-selected HMBC spectrum [41] of compound 17 revealed five 1,2 JC,H couplings: C-20 of the ester group at δ 208.9 ppm coupled with H-17 at δ 2.56 ppm, CO2 of the ester group at δ 165.9 ppm with Holefinic-1' at δ 7.62 ppm, C-3'' aromatic carbon atom at δ 114.8 ppm with H-2'' at δ 7.65 ppm, C-2'' at δ 129.2 ppm with Holefinic-2' at δ 7.53 ppm, in addition to a 1,2 JCH coupling between Colefinic-1' at δ 116.1 ppm and Holefinic-2' at δ 7.53 ppm. Further, the olefinic protons H-1' at δ 7.62 ppm showed a 1,3 JCH coupling with CO2 at δ 165.9 ppm, while two 1,3 JCH couplings between the aromatic proton H-6'' at δ 7.65 ppm and C-4'' at δ 156.6 ppm as well as Holefinic-1' proton at δ 7.62 ppm and C-1'' at δ 133.7 ppm were observed (Figure 2). The structure of compound 21 was elucidated from its 1 H and 13 C NMR spectra.…”

Section: Chemistrymentioning

confidence: 97%

“…Steroidal compounds display a variety of biological [1][2][3] functions and play a very important role in life [4][5][6], and attracted profound attention for development of potent pharmacological agents for treatments of various diseases [7] including: cardiovascular disease [8], adrenal insufficiencies [9], autoimmune disorders [10], fungal and microbial infections [11,12]. Furthermore, different steroidal derivatives have been considered as potent anti-cancer agents for the treatment of leukemia [7], breast cancer [13][14][15], prostate cancer [16] and brain tumors [17].…”

Section: Introductionmentioning

confidence: 99%

Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study

2015

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A new series of (5-pregnen-20-on-3α-yl)-substituted-benzoate analogues (10-13), (5-pregnene-20-on-3α-yl)-3-(substituted)acrylate derivatives (17-19) as well as the (17-(2-acetoxyacetyl)pregen-3α-yl)-3,4,5-trihydroxybenzoate (21) were synthesized from the β-pregenenolone scaffolds, by applying Mitsunobu reaction. All new compounds were characterized by 1 H, 13 C and 2D NMR spectroscopy. The inversion in configuration at C-3 during the formation of α-ester analogues was confirmed by NOESY NMR spectroscopy. The new compounds were evaluated for their in vitro antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells. Compounds 18 showed an EC50 value of >1.95 mg/mL. In addition, preliminary structure-activity relationship and molecular modeling of compound 18 has been studied.

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Biological transformations of steroidal compounds: A review

Cited by 148 publications

References 101 publications

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

Chemical Synthesis of Uncommon Natural Bile Acids: The 9α-Hydroxy Derivatives of Chenodeoxycholic and Lithocholic Acids

Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study

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