1232-73-1

Usage

Uses

Used in Pharmaceutical Industry:
(3b,16a)-3,16-dihydroxy-Androst-5-en-17-one is used as a pharmaceutical intermediate for the synthesis of various steroidal drugs. Its unique structure and metabolic relationship with DHEA make it a valuable compound for developing new therapeutic agents with potential applications in treating hormonal imbalances, inflammatory conditions, and other diseases.
Used in Research Applications:
As a metabolite of DHEA, (3b,16a)-3,16-dihydroxy-Androst-5-en-17-one serves as an important research tool for studying the biosynthesis, metabolism, and biological effects of steroidal compounds. It can be used in laboratory settings to investigate the mechanisms of steroid hormone action, as well as to develop and optimize analytical methods for detecting and quantifying steroidal metabolites in biological samples.
Used in Nutraceutical Industry:
(3b,16a)-3,16-dihydroxy-Androst-5-en-17-one may also have potential applications in the nutraceutical industry as a dietary supplement or ingredient in health products. Its association with DHEA suggests that it could have beneficial effects on health and well-being, although further research is needed to fully understand its potential benefits and optimal dosages for human consumption.

InChI:InChI=1/C19H28O3/c1-18-7-5-12(20)9-11(18)3-4-13-14(18)6-8-19(2)15(13)10-16(21)17(19)22/h3,12-16,20-21H,4-10H2,1-2H3/t12-,13+,14-,15-,16+,18-,19-/m0/s1

Upstream product

• 105119-96-8 16α-chloro-3β-hydroxy-5-androsten-17-one 
• 74644-60-3 16β-bromo-3β-hydroxy-5-androsten-17-one 
• 1093-91-0 3β-hydroxy-16α-bromoandrost-5-ene-17-one 
• 10459-30-0 3β,16α-dihydroxy-17,17-dimethoxyandrost-5-ene 
• 17134-39-3 16α-iodo-3β-hydroxy-5-androsten-17-one 
• 53-43-0 dehydroepiandrosterone 
• 25256-95-5 3β,17β-Diacetoxy-androsta-5,16-diene 
• 24335-49-7 3β-acetoxy-16α-bromoandrost-5-en-17-one 
• 880517-89-5 17,17-dimethoxyandrost-5-ene-3β,16α-diyl diacetate 

Downstream Products

• 1159-66-6 (R)-3,17-Dihydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,17-tetradecahydro-cyclopenta[a]phenanthren-16-one 
• 113999-82-9 3β,16α-diacetoxy-7α-hydroxy-androst-5-en-17-one 
• 115963-65-0 3β,7α,16α-triacetoxy-androst-5-en-17-one 
• 165181-92-0 3β,7α,17β-trihydroxyandrost-5-en-16-one 
• 1159-66-6 3β,17β-dihydroxyandrost-5-en-16-one 

Relevant academic research and scientific papers

CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.

Derivatives of 16α-hydroxy-dehydroepiandrosterone with an additional 7-oxo or 7-hydroxy substituent: Synthesis and gas chromatography/mass spectrometry analysis

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.

Identification and phenotype characterization of two CYP3A haplotypes causing different enzymatic capacity in fetal livers

Background: The fetal liver cytochrome P450 (CYP) 3A enzymes metabolize potentially toxic and teratogenic substrates and drugs in addition to endogenous hormones and differentiation factors. CYP3A7 is the most abundant CYP in the human liver during fetal stages and the first months of postnatal age and shows a large interindividual variability of unknown molecular basis. Methods: A new variant gene (CYP3A7* (*)2), which carries a mutation in exon 11 of CYP3A7 causing a T409R substitution, was identified by direct sequencing. Genotype analysis was performed by use of polymerase chain reaction followed by restriction enzyme analysis. CYP3A7.2 activity was assessed in heterologous expression systems and human fetal liver microsomes. Results: The frequency of CYP3A7* (*)2 was 8%, 17%, 28%, and 62% in white, Saudi Arabian, Chinese, and Tanzanian individuals, respectively. By use of human HEK293 cells, no significant differences in expression between CYP3A7.1 and CYP3A7.2 were found and fetal livers homozygous for CYP3A7* (*)2 had similar or higher CYP3A7 protein contents than CYP3A7* (*)1 livers. Kinetic studies showed that CYP3A7.2 was a functional enzyme with a significantly higher catalytic constant (kcat) as compared with CYP3A7.1 (P a linkage disequilibrium between the CYP3A7* (*)2 and CYP3A5* (*)1 alleles that was subject to interethnic differences. Determination of the alprazolam 1-hydroxylation rate revealed that CYP3A5 plays a significant role in the metabolism of CYP3A substrates in the fetal liver. Conclusion: We have identified 2 different CYP3A phenotypes in the fetal liver--one that is the result of a CYP3A7* (*)1/CYP3A5* (*)3 haplotype causing CYP3A7.1 but no CYP3A5 expression and another with higher detoxification capacity, inherent in the CYP3A7* (*)2/CYP3A5* (*)1 haplotype, where CYP3A5 and a more active form of CYP3A7 are expressed. Copyright

Novel steroid inhibitors of glucose 6-phosphate dehydrogenase

Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially developed; the 3β-alcohol can be replaced with 3β-H-bond donors such as sulfamide, sulfonamide, urea, and carbamate. Improved potency was achieved by replacing the androstane nucleus with a pregnane nucleus, provided a ketone at C-20 is present. For pregnan-20-ones incorporation of a 21-hydroxyl group is often beneficial. The novel compounds generally have good physicochemical properties and satisfactory in vitro DMPK parameters. These derivatives may be useful for examining the role of G6PD inhibition in cells and will assist the future design of more potent steroid inhibitors with potential therapeutic utility.

Novel components of the human metabolome: The identification, characterization and anti-inflammatory activity of two 5-androstene tetrols

Two natural 5-androstene steroid tetrols, androst-5-ene-3β,7β, 16α,17β-tetrol (HE3177) and androst-5-ene-3α,7β,16α, 17β-tetrol (HE3413), were discovered in human plasma and urine. These compounds had significant aqueous solubility, did not bind or transactivate steroid-binding nuclear hormone receptors, and were not immunosuppressive in murine mixed-lymphocyte studies. Both compounds appear to be metabolic end products, as they were resistant to primary and secondary metabolism. Both were orally bioavailable, and were very well tolerated in a two-week dose-intensive toxicity study in mice. Anti-inflammatory properties were found with exogenous administration of these compounds in rodent disease models of multiple sclerosis, lung injury, chronic prostatitis, and colitis.

DRUGS AND USES

The invention relates to methods to treat specified clinical disorders such as hyperglycemia, type 2 diabetes, arthritis and multiple sclerosis. The invention also provides methods to identify and characterize drugs, which are characterized in part by eliciting a variable biologic or therapeutic effect on a biomolecule at one time and relative normalization of the biomolecule at another time point. Compounds include 17α-ethynylandrost-5-ene-3β,7β, 17β-triol or androst-5-ene-3β,4β, 16α, 17β-tetrol, which can be used as reference standards to facilitate assessing and characterizing such candidate drugs.

C19-Steroids as androgen receptor modulators: Design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists

Dehydroepiandrosterone (DHEA), the most abundant steroid in human circulating blood, is metabolized to sex hormones and other C19-steroids. Our previous collaborative study demonstrated that androst-5-ene-3β,17β-diol (Adiol) and androst-4-ene-3,17-dione (Adione), metabolites of DHEA, can activate androgen receptor (AR) target genes. Adiol is maintained at a high concentration in prostate cancer tissue; even after androgen deprivation therapy and its androgen activity is not inhibited by the antiandrogens currently used to treat prostate cancer patients. We have synthesized possible metabolites of DHEA and several synthetic analogues and evaluated their role in androgen receptor transactivation to identify AR modulators. Steroids with low androgenic potential in PC-3 cell lines were evaluated for anti-dihydrotestosterone (DHT) and anti-Adiol activity. We discovered three potent antiandrogens: 3β-acetoxyandrosta-1,5-diene-17-one 17-ethylene ketal (ADEK), androsta-1,4-diene-3,17-dione 17-ethylene ketal (OAK), and 3β-hydroxyandrosta-5,16-diene (HAD) that antagonized the effects of DHT as well as of Adiol on the growth of LNCaP cells and on the expression of prostate-specific antigen (PSA). In vivo tests of these compounds will reveal their potential as potent antiandrogens for the treatment of prostate cancer.

Reactions of Enolizable Steroidal 4-En-3-ones and 17-Ones with Hypervalent Iodine

Reaction of the 3-oxo-4-androsten-derivative 1 or 4 with 1.2 eq. of o-iodosylbenzoic acid in methanolic KOH gave the methoxy products, the 4-methoxide 2 or 5 and the 6β-methoxide 3 or 6, along with dehydrated compound, the 4,6-dienone 7 or 8, respectively.Treatment of the 6-methoxide 3 or 6 with trimethylsilyl iodide yielded the 5α-androstane-3,6-dioxo derivative 11 or 12 in high yield.The same hypervalent oxidation of the 17-oxo steroid 15, 18, 21 or 24 using excess iodine and a longer reaction time produced the corresponding 16α-hydroxy-17,17-dimethylacetal 16, 19,22 or 25, which was converted into the 16α-hydroxy-17-one 17, 20, 23 or 26 by treatment with diluted HCl in every case.Keywords - hypervalent iodine oxidation; o-iodosylbenzoic acid; 4-en-3-oxo steroid; 17-oxo steroid; methoxylation; dehydration; 16α-hydroxy-17,17-dimethoxy steroid; 16α-hydroxy-17-oxo steroid; 5α-saturated 3,6-dioxo steroid

Stereoselective hydrolysis of 16α-halo-17-keto steroids and long-range substitution effects on the hydrolysis of 16α-bromo-17-ketones and 2α-bromo-3-ketones

Epimerization of 16α-chloro- (1a), bromo- (1b), and iodo-3β-hydroxy-5-androsten-17-one (1c) by a brief treatment with 0.2 equiv NaOH in aqueous pyridine reached equilibrium between 16α- and 16β-halo ketones. 16α-/16β-Halo ketone ratios at equilibrium were 1.5 for Cl, 1.25 for Br, and 1.0 for I. Kinetic analysis showed that compounds 1a-c were stereoselectively converted to the corresponding 16α-hydroxy derivative 3 by an S(N)2 mechanism, in which the order of the apparent reactivity was Br > I > Cl. The hydrolysis of a number of 16α-bromo-17-ketones and 2α-bromo-3-ketones was carried out. The yields of the corresponding alcohols were found to depend on remote structural features in the steroids.

Stereospecific Synthesis of 16α-Hydroxy-17-oxo Steroids by Controlled Alkaline Hydrolysis of Corresponding 16-Bromo 17-Ketones and Its Reaction Mechanism

Synthesis of 16α-hydroxy-17-oxo steroids 3, 5b, and 3β,16α-dihydroxy-5-17-oxoandrosten-3-yl sulfate (7) from 16α-bromo-17-oxo steroids 1, 5a, and 6a and the reaction mechanism of the controlled alkaline hydrolysis are described.Treatment of the bromo ketones with NaOH in aqueous DMF gave the 16α-hydroxy 17-ketones stereoselectively in 95percent yield without formation of other ketols.The sodium salt of 3-sulfate 7 was also obtained in one step in 85percent yield from the corresponding bromo ketone (1a).Isotope-labeling experiments and time-course studies showed that equilibration between the 16-bromo epimers 1 and 2 precedes the formation of 3, in which the true intermediate is 2 and not 1, and that the ketol 3 is formed by the direct SN2 displacement of the 16β-bromine.The 16β-morpholino derivative 8 obtained by reaction of 1 with morpholine was shown to be an isomerized product of the 16α isomer which is produced also by SN2 displacement of the 16β-bromine.The mechanism of ketol rearrangement of 3 to the 17β-hydroxy-16-oxo compound 4 was found to involve a hydration to the carbonyl function.The new hydration-dehydration mechanism is proposed for the ketol rearrangement.