53-43-0

Basic information

• Product Name: Dehydroepiandrosterone
• Synonyms: PRASTERONE;TRANS-DEHYDROANDROSTERONE;ANDRO-3B-OL-17-ONE;ANDROSTENOLONE;3-HYDROXYANDROST-5-EN-17-ONE;3BETA-HYDROXYANDROST-5-EN-17-ONE;3B-HYDROXY-5-ANDROSTEN-17-ONE;3BETA-HYDROXY-5-ANDROSTEN-17-ONE
• CAS NO: 53-43-0
• Molecular Formula: C19H28O2
• Molecular Weight: 288.42
• EINECS: 200-175-5
• Product Categories: Pharmaceutical Intermediates;Steroids;17-Ketosteroids;Biochemistry;Hydroxyketosteroids;Nutritional Supplements;Intermediates & Fine Chemicals;Pharmaceuticals;Steroid and Hormone;API;Inhibitors
• Mol File: 53-43-0.mol

Chemical Properties

• Melting Point: 149-151 °C(lit.)
• Boiling Point: 370.65°C (rough estimate)
• Flash Point: 9℃
• Appearance: White/Fine Crystalline Powder
• Density: 1.0484 (rough estimate)
• Vapor Pressure: 4.54E-09mmHg at 25°C
• Refractive Index: 1.4709 (estimate)
• Storage Temp.: Hormones
• Solubility: insoluble in H2O; ≥13.7 mg/mL in DMSO; ≥58.6 mg/mL in ETOH
• PKA: 15.02±0.60(Predicted)
• Water Solubility: 21.8mg/L(23.5 oC)
• Merck: 2871
• BRN: 2058110
• CAS DataBase Reference: Dehydroepiandrosterone(CAS DataBase Reference)
• NIST Chemistry Reference: Dehydroepiandrosterone(53-43-0)
• EPA Substance Registry System: Dehydroepiandrosterone(53-43-0)

Safety Data

• Hazard Codes: Xi,T,F
• Statements: 36/37/38-39/23/24/25-23/24/25-11
• Safety Statements: 26-36-24/25-45-36/37-16-7
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 2
• RTECS: BV8396000
• Hazardous Substances Data: 53-43-0(Hazardous Substances Data)

Usage

Uses

Used in Menopausal Syndrome Treatment:
Dehydroepiandrosterone is used as a treatment for menopausal syndrome, providing relief from symptoms associated with hormonal imbalances.
Used in HIV Management:
People living with HIV may take DHEA for various reasons, including treatment of depression, increasing bone density, decreasing arterial plaques, improving immune function, enhancing memory, and increasing muscle strength.
Used in Dietary Supplements:
DHEA is a popular nonprescription oral dietary supplement used by men to enhance cognitive function, mood, libido, and athletic performance. It was reclassified as a nutritional supplement after the passage of the Dietary Supplement Health and Education Act of 1994.
Used in Pharmaceutical Industry:
Dehydroepiandrosterone is used as an active pharmaceutical ingredient in various medications, targeting a range of health issues.
Used in Research and Development:
DHEA is utilized in research and development for its potential applications in various fields, including neuroscience, endocrinology, and sports medicine.
Used in Cosmetics:
Dehydroepiandrosterone may be used in the cosmetics industry for its potential anti-aging and skin health benefits.
Occurrence:
DHEA is naturally occurring in yam (see Wild Yam, p. 596-597).
Chemical Properties:
Dehydroepiandrosterone is a white fine crystalline powder with two crystal forms. It is soluble in alcohol, ether, benzene, slightly soluble in chloroform, and petroleum ether.
Brand Names:
Some brand names for Dehydroepiandrosterone include 17-chetovis, 17-hormoforin, Cetavister, Climatost, Dastonil, Dha-s (prasterone), Gynodian, Longevital 5000, Maxepa, Mentalormon, Mylis, Neurocotex, Psicosterone, Ro 66827, SH 833, and Ultrapla.

Indications and Usage

Dehydroepiandrosterone (DHEA,) chemical name 3β-hydroxy-5alpha-androstane-17-ketone, is an esterifying 3–β–hydroxy steroid retaining 5,6 cholesterol. A white crystalline powder, soluable in ethanol, ether, and benzene, and slightly soluable in chroloform and petroleum ether. Precipitates in digitalis. DHEA is an estrogen precursor secreted by the reticular layer of the human adrenal cortex. Prevents obesity, resists diabetes, fights cancer, fights cortical disease, and delays senility treats immune deficiencies, promotes the growth and differentiation of bone cells, and promotes the synthesis of protein. It also resists viral infections, improves memory, and relieves nervous tension. DHEA is the main ingredient in steroid hormone intermediates (such as norethindrone and bisacetylene, etc.) and in birth control, and is involved in the secretion of many adrenal hormones. It has undergone extensive clinical research on treating menopausal syndrom, chorionitis, coronary heart disease, gout, psoriasis, AIDS and so on.

Mechanisms of Action

DHEA has a thyroid stimulating effect inhibiting food and fat intake and reducing fat accumulation, etc. It improves glucose tolerance, increases insulin level and fights diabetes. It can enhance endocrine system actiity, reduce cortisol levels, and resist a variety of pathological processes. It can help the body obtain cortical antibodies. DHEA has a strong protective and synergistic effect when used to treat tumors, becuase it inhibits ribose 5-phosphate. Inhibits cancer by inhibiting excessive mitochondria (NADPH) and ribose 5-phosphate esters. Regulates the growth of pancreatic cancer cells by regulating the concentration of estrogen in blood plasma. A decline in GnRH gene expression leads to aging, and DHEA can restore GnRH neuronal activity, stopping or improving certain diseases associated with declines in DHEA by stimulating GnRH biosynthesis. Restores impaired immune response, improves T- and B-cell function, and plays an important role in enhancing the physiological activity of insulin-like growth factor (IGF-1,) and is a potentially useful drug for immunodeficiency. DHEA alone cannot directly affect the growth and differential of osteoblasts, but it can do so by influencing 1,25-dihydroxyvitamin D3. The effects of DHEA on bone mass depend on the presence and form of sex hormones in bone cells and their endrocine effects on osteoblasts. DHEA is an anabolic protein hormone which promotes protein synthesis. According to the findings of Marrero and others, feeding DHEA (0.45%) to mice increased liver weight, increasing liver mitochondria by guiding liver protein restoring RNA and protein synthesis.

Originator

Aslera ,Genelabs Technologies, Inc.

Manufacturing Process

To a solution of 1 gram of 16-dehydropregnenolon-3β-acetate in 10 ml pyridine is added 0.22 gram of hydroxylamine hydrochloride, and the mixture is allowed to stand at room temperature for four days. One gram of 16dehydropregnenolon-3β-acetate oxime is dissolved in 30 ml of hot dioxane, and then the solution is cooled in an ice bath until about one-half of the dioxane has solidified. Then 1 gram of phosphorus pentachloride is added and the mixture is shaken until all the dioxane has melted. The mixture is maintained at 35°C, for seventy-five minutes, then an excess of ice is added and the solution is again allowed to stand at 35°C. After about thirty minutes, a solution of 5 ml of concentrated hydrochloric acid in 10 ml of water is added, and the mixture is diluted with water, extracted with ether and the ethereal extract washed with dilute sodium hydroxide solution. The ether is removed on a steam bath and the residue is worked up to yield dehydroepiandrosterone.

Therapeutic Function

Glucocorticoid

World Health Organization (WHO)

The World Health Organization has no information further to the above regarding preparations containing prasterone or to indicate that such preparations remain available.

Health Hazard

An experimental teratogen.Experimental reproductive effects. Questionablecarcinogen with experimental neoplastigenic data. Whenheated to decomposition it emits acrid smoke andirritating fumes.

Biochem/physiol Actions

Product does not compete with ATP.

Side effects

Side effects may include acne, skin rash, GI upset, hirsuitism, hypertension, and increased HDL. In people with HIV, additional side effects may include fatigue, nasal congestion, and headaches.

Safety

Dehydroepiandrosterone should always be used under the supervision of a medical professional. It is likely safe for people with low DHEA levels to take oral supplements short-term (<6 months) to restore DHEA to normal, but long-term use and doses resulting in high DHEA levels are possibly unsafe. Side effects are often seen with higher doses and longterm use.

references

[1]. kimonides vg, khatibi nh, svendsen cn, et al. dehydroepiandrosterone (dhea) and dhea-sulfate (dheas) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. proc natl acad sci u s a, 1998, 95(4): 1852-1857.[2]. suzuki m, wright ls, marwah p, et al. mitotic and neurogenic effects of dehydroepiandrosterone (dhea) on human neural stem cell cultures derived from the fetal cortex. proc natl acad sci u s a, 2004, 101(9): 3202-3207.[3]. charalampopoulos i, tsatsanis c, dermitzaki e, et al. dehydroepiandrosterone and allopregnanolone protect sympathoadrenal medulla cells against apoptosis via antiapoptotic bcl-2 proteins. proc natl acad sci u s a, 2004, 101(21): 8209-8214.

InChI:InChI=1/C19H28O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h3,13-16,20H,4-11H2,1-2H3/t13-,14-,15?,16?,18-,19-/m0/s1

Synthetic route

prasterone acetate (853-23-6) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With sodium hydroxide In methanol	98.54%
With methanol; sodium hydroxide at 40℃; for 4h; Inert atmosphere;	94.8%
With potassium hydroxide In ethanol

(1aR,3aR,3bS,5aS,8aS,8bR,10aR)-10-Hydroxy-3a,5a-dimethyl-tetradecahydro-cyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-one (1028084-93-6) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With Me3SiN=CMe(1+)*BF4(1-); water In acetonitrile	96%

Acetic acid (1aR,3aR,3bS,5aS,8aS,8bR,10aR)-3a,5a-dimethyl-6-oxo-hexadecahydro-cyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-10-yl ester (24357-31-1, 58691-91-1) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With Me3SiN=CMe(1+)*BF4(1-); water In acetonitrile	96%

(17Ξ)-spiro[androst-5-en-17,2'-[1,3]oxathiolan]-3β-ol (327622-68-4) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With N-Bromosuccinimide; water In acetone at 20℃; for 8h; Hydrolysis;	88%

3β-[2-(triphenylsilyl)ethoxycarbonyloxy]androst-5-en-17-one (1310361-06-8) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With tetrabutyl ammonium fluoride; cesium fluoride In tetrahydrofuran at 0℃; for 0.166667h; Inert atmosphere;	88%

5-androsten-3β,17α-diol-17-carboxylic acid (81481-38-1) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With sodium hydroxide; sodium hypochlorite In diethyl ether 1.) 0 deg C -> room temperature, 2.) room temperature, 3 h;	85%

Androstenedione (63-05-8) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
Stage #1: Androstenedione With titanium(IV) oxide; platinum In toluene at 100℃; for 3h; Stage #2: With hydrogen In toluene under 15001.5 Torr; for 8h; Temperature; Reagent/catalyst; Pressure;	85%
Multi-step reaction with 2 steps 1.1: potassium tert-butylate / tert-butyl alcohol / 1.5 h / 35 - 40 °C / Inert atmosphere 1.2: 20 - 25 °C 2.1: NADP; magnesium(II) chloride hexahydrate; alpha-D-glucopyranose; NAD+ / 2-methyltetrahydrofuran; aq. phosphate buffer / 20 - 32 °C / Enzymatic reaction View Scheme
Multi-step reaction with 2 steps 1: potassium tert-butylate / tert-butyl alcohol / 1 h / 30 - 35 °C / Inert atmosphere 2: D-glucose; NAD; glucose dehydrogenase (CDX-901)_; ketoreductase from Sphingomonas wittichii; potassium carbonate / ethyl acetate; aq. phosphate buffer / 21 h / 32.5 °C / pH 6.3 - 6.5 / Inert atmosphere; Enzymatic reaction View Scheme
Multi-step reaction with 4 steps 1: aluminum (III) chloride; 5-sulfosalicylic Acid / 5 h / 20 - 30 °C / Inert atmosphere; Large scale 2: orthoformic acid triethyl ester; boron trifluoride diethyl etherate / dichloromethane / 5 h / 20 - 30 °C / Inert atmosphere 3: calcium borohydride / dichloromethane / 15 h / -20 - -15 °C 4: toluene-4-sulfonic acid / acetone; water / 1 h / 45 - 50 °C / Inert atmosphere View Scheme

17-oxo-androst-5-en-3β-yl Se-phenyl selenocarbonate (76920-40-6) → dehydroepiandrosterone (53-43-0) + 3β-formyl-oxy-5-androsten-17-one (29163-23-3) + 5-androsten-17-one (25824-80-0)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene at 80℃;	A 9% B 76% C 5%
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In 1,3,5-trimethyl-benzene at 164℃;	A 10% B 28% C 62%

3-tetrahydropyran-2-yloxy-androst-5-en-17-one (19637-35-5) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With silica gel; copper(II) sulfate In dichloromethane for 24h; Heating;	70%

3β-acetoxy-20-hydroxyiminopregna-5,16-diene (23549-24-8, 23549-26-0, 2174-13-2) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
Stage #1: 3β-acetoxy-20-hydroxyiminopregna-5,16-diene With pyridine; trichlorophosphate at 0 - 20℃; for 3h; Inert atmosphere; Stage #2: With methanol; sodium hydroxide for 12h; Reflux;	64%
Stage #1: 3β-acetoxy-20-hydroxyiminopregna-5,16-diene With pyridine; trichlorophosphate In toluene at 10 - 20℃; for 4h; Bechmanns' reaction; Stage #2: With potassium hydroxide In methanol Heating;	51.8%
With pyridine; trichlorophosphate at -5℃; Beckmann rearrangement;
Multi-step reaction with 2 steps 1: phosphorus (III) oxychloride 2: potassium hydroxide / methanol View Scheme

16α-iodo-3β-hydroxy-5-androsten-17-one (17134-39-3) → dehydroepiandrosterone (53-43-0) + 16α-hydroxy dehydroepiandrosterone (1232-73-1)

Conditions	Yield
With sodium hydroxide In pyridine; water for 1h;	A 20% B 60%
With sodium hydroxide In pyridine; water for 1h;	A 20% B 60%
With sodium hydroxide In pyridine; water for 1h; Mechanism; var. of NaOH conc. and time;	A 20% B 60%

Trifluoro-methanesulfonic acid (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester → dehydroepiandrosterone (53-43-0) + bis(3β-androst-5-en-17-one) ether (66147-28-2)

Conditions	Yield
With 1,2,2,6,6-pentamethylpiperidine In water Heating;	A 60% B 40%

3β-O-(tetrahydropyranyl)-17-cycloethylenedioxy-androst-5-ene → dehydroepiandrosterone (53-43-0) + 3β-hydroxy-17,17-ethylenedioxo-5-androstene (7745-40-6, 14456-21-4) + 3-tetrahydropyran-2-yloxy-androst-5-en-17-one (19637-35-5)

Conditions	Yield
With silica gel; copper(II) sulfate In benzene at 25℃; for 40h;	A 17% B 59% C 2%
With silica gel; copper(II) sulfate In chloroform at 25℃; for 40h;	A 51% B 6% C 30%

C28H47NO2 → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0℃; for 0.166667h;	46%

Phenylselenyl bromide (34837-55-3) + androstenone hydrazone (63015-10-1, 77059-27-9) → dehydroepiandrosterone (53-43-0) + 17-bromo-3β-hydroxy-17-selenophenylandrost-5-ene (114474-49-6) + 3β-hydroxy-17-phenylselenoandrosta-5,16-diene (91414-16-3)

Conditions	Yield
With pyridine In tetrahydrofuran	A 45% B 8% C 20%

5-androstene-3β,17β-diol 3-acetate 17-p-toluene-δ-sulfonate (1259-22-9) → dehydroepiandrosterone (53-43-0) + androst-5-ene-3β,17α-diol (1963-03-7) + 17β-methyl-18-norandrosta-5,13-diene-3β-ol (82309-44-2) + 17-methyl-18-norandrosta-5,13(17)-diene-3β-ol (23930-65-6)

Conditions	Yield
With potassium acetate In dimethyl sulfoxide at 100℃; for 6h;	A 25% B 41% C n/a D n/a

17-(N-2-pyridylmethyl)imino-3β-hydroxy-androst-5-ene → dehydroepiandrosterone (53-43-0) + (-)-3β,12β-dihydroxyandrost-5-ene-17-one (828938-19-8)

Conditions	Yield
Multistep reaction;	A 22% B 35%

cholesterol (57-88-5) → dehydroepiandrosterone (53-43-0) + Androstenedione (63-05-8)

Conditions	Yield
With [2,2]bipyridinyl; Cephalosporium longisporum; Micrococcus sp; Pseudomonas stutzeri at 29℃; for 72h;	A 27% B 6%

17-(N-2-pyridylmethyl)imino-3β-hydroxy-androst-5-ene → dehydroepiandrosterone (53-43-0) + 12β-chloro-3β-hydroxy-androst-5-en-17-one + (-)-3β,12β-dihydroxyandrost-5-ene-17-one (828938-19-8)

Conditions	Yield
Multistep reaction;	A 21% B 19% C 25%

Pregnenolone (145-13-1) → dehydroepiandrosterone (53-43-0) + 17α-Hydroperoxy-5-pregnen-3β-ol-20-on (34069-59-5)

Conditions	Yield
With 18-crown-6 ether In tetrahydrofuran; benzene at 18℃; under 760 Torr; for 24h;	A 23% B 9%

Pregnenolone (145-13-1) → dehydroepiandrosterone (53-43-0) + 5-androstenediol (521-17-5, 1963-03-7, 4593-57-1, 4593-58-2, 14504-94-0, 16895-59-3, 47122-33-8, 64162-67-0, 75767-22-5, 139973-51-6, 151284-19-4) + 3β,15β-dihydroxy-5-androsten-17-one

Conditions	Yield
With Gelasinospora retispora GRK002 In methanol; water at 34℃; for 336h; pH=5; Microbiological reaction;	A 23% B 18% C 11%

Pregnenolone (145-13-1) → dehydroepiandrosterone (53-43-0) + 17-Hydroxypregnenolone (387-79-1)

Conditions	Yield
With potassium phosphate buffer; α-D-glucose 6-phosphate; NADP; phosphatidylcholine Mechanism; pig 17α-hydroxylase-17,20-lyase, NADPH-cytochrome-P-450-reductase, glucose-6-phosphate dehydrogenase, pH 7.2; also in the presence of cytochrome b5 or bovine tests microsomes; also 3β-hydroxyandrost-5-ene-17β-carbaldehyde;	A 16% B 21%

cholesterol (57-88-5) → dehydroepiandrosterone (53-43-0)

β-sitosterol (83-46-5) → dehydroepiandrosterone (53-43-0)

dehydroepiandrosterone sulfate (651-48-9) → dehydroepiandrosterone (53-43-0) + 6β-hydroxy-3α,5-cycloandrostan-17-one (663-39-8, 24357-32-2, 57236-38-1, 118013-84-6)

Conditions	Yield
Ausbeute in gepufferten wss. Loesungen (pH 1.2-6.8);

5-androstenedione (571-36-8) → dehydroepiandrosterone (53-43-0) + 3α-hydroxy-androst-5-en-17-one (2283-82-1)

Conditions	Yield
With ethanol; nickel Hydrogenation;

3β-benzoyloxy-androst-5-en-17-one (83205-52-1, 2080-86-6) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With potassium hydroxide
With potassium hydroxide

17β-Aminoandrost-5-en-3β-ol (4350-66-7) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With diethyl ether; hypochloric acid; sodium sulfate at 0℃; Erwaermen des Reaktionsprodukts mit Natriumaethylat und Aethanol und Behandeln des Reaktionsloesung mit wss.H2SO4;

3β,17-dihydroxy-androst-5-ene-17α-carbonitrile (35060-03-8) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
unter vermindertem Druck;
at 110 - 120℃;

3β-acetoxy-20-methyl-pregnadiene-(5,17(20)) (60446-55-1) → dehydroepiandrosterone (53-43-0)

Conditions	Yield
With chloroform; bromine anschliessendes Behandeln mit Ozon; Erhitzen des erhaltenen Reaktionsprodukts mit Zink-Pulver und Essigsaeure und Hydrolysieren des isolierten 3β-Acetoxy-androsten-(5)-ons-(17);
With potassium permanganate; acetic acid at 50℃; Erhitzen des erhaltenen Reaktionsprodukts mit Zink-Pulver und Essigsaeure und Hydrolysieren des isolierten 3β-Acetoxy-androsten-(5)-ons-(17);

formic acid (64-18-6) + dehydroepiandrosterone (53-43-0) → 3β-formyl-oxy-5-androsten-17-one (29163-23-3)

Conditions	Yield
In water for 19h;	100%
at 20 - 25℃; for 4h;	100%
for 5h; Reflux;	89.3%
for 5h; Reflux;

dehydroepiandrosterone (53-43-0) → Epiandrosterone (481-29-8)

Conditions	Yield
With palladium on activated charcoal; hydrogen In ethanol at 20℃; under 2068.65 Torr; Inert atmosphere;	100%
With palladium on activated charcoal; hydrogen In ethanol under 2068.65 Torr;	100%
With palladium 10% on activated carbon; hydrogen In ethanol at 40℃; under 2068.65 Torr; for 12h;	99%

dehydroepiandrosterone (53-43-0) + acetic anhydride (108-24-7) → prasterone acetate (853-23-6)

Conditions	Yield
With toluene-4-sulfonic acid for 0.0111667h; microwave irradiation;	100%
With dmap; triethylamine In dichloromethane at 20℃; for 5h;	100%
With dmap; triethylamine In dichloromethane at 20℃; for 5h;	100%

dehydroepiandrosterone (53-43-0) + ethylene glycol (107-21-1) → 3β-hydroxy-17,17-ethylenedioxo-5-androstene (7745-40-6, 14456-21-4)

Conditions	Yield
With camphor-10-sulfonic acid In toluene at 111℃;	100%
With toluene-4-sulfonic acid In benzene for 4.5h; Heating;	99%
With camphor-10-sulfonic acid In cyclohexane for 20h; Reflux;	99%

dehydroepiandrosterone (53-43-0) + tert-butyldimethylsilyl chloride (18162-48-6) → (3S)-3-tert-butyldimethylsilyloxyandrost-5-en-17-one (42151-23-5)

Conditions	Yield
With dmap In dichloromethane 1.) 0 deg C, 1 h, 2.) room temperature, 16 h;	100%
With dmap; triethylamine In dichloromethane at 20℃; for 15h;	100%
With 1H-imidazole In dichloromethane at 25℃; for 12h;	99%

dehydroepiandrosterone (53-43-0) + diethyl dicarbonate (1609-47-8) → 3β-ethoxycarbonyloxyandrost-5-en-17-one (86270-42-0)

Conditions	Yield
for 0.5h; Heating;	100%

dehydroepiandrosterone (53-43-0) + tert-butylchlorodiphenylsilane (58479-61-1) → (3S,10R,13S)-3-((tert-butyldiphenylsilyl)oxy)-10,13-dimethyl-3,4,7,8,9,10,11,12,13,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17(2H)-one (191677-71-1)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide for 120h; Ambient temperature;	100%
With impramine	99%
With 1H-imidazole In dichloromethane at 0 - 20℃; for 5h;	98%

chloro-trimethyl-silane (75-77-4) + dehydroepiandrosterone (53-43-0) → PdCl2(PPh3)2 (3747-91-9)

Conditions	Yield
With pyridine In N,N-dimethyl-formamide at 0 - 20℃; for 2.16667h; Inert atmosphere;	100%
With triethylamine In tetrahydrofuran at 20℃;	97%
Stage #1: dehydroepiandrosterone With 1H-imidazole In dichloromethane at 20 - 30℃; for 0.0833333h; Stage #2: chloro-trimethyl-silane In dichloromethane at 20 - 30℃; for 2h; Reagent/catalyst;	81.6%

dehydroepiandrosterone (53-43-0) + 2,2-Dimethyl-1,3-propanediol (126-30-7) → (3S,8R,9S,10R,13S,14S)-5',5',10,13-tetramethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydrospiro[cyclopenta[a]phenanthrene-17,2'-[1,3]dioxan]-3-ol

Conditions	Yield
With camphor-10-sulfonic acid In cyclohexane at 85℃; for 16h; Dean-Stark;	99.8%

dehydroepiandrosterone (53-43-0) → dehydroepiandrosterone-17-hydrazone (63015-10-1)

Conditions	Yield
With barium sulfate; hydrazine hydrate In ethanol; water at 20 - 30℃; for 12h; Large scale;	99.2%
With sulfuric acid; hydrazine hydrate In ethanol at 20℃; for 40h;	98.7%
Stage #1: dehydroepiandrosterone With hydrazine hydrate In ethanol at 35℃; Stage #2: With hydrazinium sulfate In ethanol at 35℃; for 20h;	98.5%

dehydroepiandrosterone (53-43-0) + chloromethyl methyl ether (107-30-2) → (3β)-3-(methoxymethoxy)-androst-5-en-17-one (18000-76-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 3.5h;	99%
With N,N-dimethyl-aniline In dichloromethane; benzene for 12h; Ambient temperature;	75%

cycloheptanoic acid (1460-16-8) + dehydroepiandrosterone (53-43-0) → 17-oxaandrost-5-ene-3β-yl cycloheptanoate (1470067-56-1)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 2h;	99%
With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 2h;	88%
With dmap; dicyclohexyl-carbodiimide In chloroform Steglich Esterification;
With dmap; dicyclohexyl-carbodiimide

dehydroepiandrosterone (53-43-0) + methanesulfonyl chloride (124-63-0) → androst-5-en-3β-ol-17-one mesylate (25810-70-2)

Conditions	Yield
With pyridine at 20 - 25℃; for 20h; Inert atmosphere;	98.4%
With pyridine at 20℃; for 24h;	76%

dehydroepiandrosterone (53-43-0) + pivaloyl chloride (3282-30-2) → (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ylpivalate (158300-47-1)

Conditions	Yield
With pyridine at 10 - 28℃; for 16.5h;	98.1%
With pyridine at 85℃; for 14h;	91%
With pyridine; dmap at 0℃; for 4h;	5.83 g

dehydroepiandrosterone (53-43-0) → androst-5-en-3β-ol (1476-64-8)

Conditions	Yield
With potassium hydroxide; hydrazine hydrate In diethylene glycol a) 120 deg C, 1 h, b) 230 deg C, 3.5 h;	98%
Stage #1: dehydroepiandrosterone With hydrazine hydrate In diethylene glycol at 130℃; for 2h; Wolff-Kishner Reduction; Stage #2: With potassium hydroxide In diethylene glycol at 210℃; for 4h; Stage #3: With sulfuric acid In water; diethylene glycol	95.8%
With chloro-trimethyl-silane; zinc In methanol; dichloromethane at 0 - 20℃; for 18h; Clemmensen Reduction;	75%

dehydroepiandrosterone (53-43-0) + benzaldehyde (100-52-7) → 16-benzylidene-17-oxo-5-androsten-3β-ol (17243-87-7, 74708-33-1)

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 1h;	98%
With methanol; potassium hydrogencarbonate
With Aliquat 336; sodium carbonate In water at 80℃; for 2.5h; Aldol Condensation;
With potassium fluoride on basic alumina In ethanol for 1h; Claisen-Schmidt Condensation; Reflux;

dehydroepiandrosterone (53-43-0) + benzoyl chloride (98-88-4) → 3β-benzoyloxy-androst-5-en-17-one (83205-52-1, 2080-86-6)

Conditions	Yield
With pyridine at 10 - 25℃; Reagent/catalyst; Temperature;	98%
With tetramethylurea at 70 - 75℃; for 3h;	78%
With pyridine at 20℃; for 12h;	76%
With pyridine

dehydroepiandrosterone (53-43-0) + iopanoic acid (96-83-3) → dehydroepiandrosterone iopanoate (83172-20-7)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	98%

dehydroepiandrosterone (53-43-0) → 3β-hydroxy-16α-bromoandrost-5-ene-17-one (1093-91-0)

Conditions	Yield
With copper(ll) bromide In methanol for 12h; Heating;	98%
With copper(ll) bromide In methanol at 70℃; for 12h;	97%
With copper(I) bromide In methanol; benzene for 4h; Heating / reflux;	62.77%

dehydroepiandrosterone (53-43-0) + 1-amino-2-propene (107-11-9) → 17β-allylamino-3β-hydroxyandrost-5-ene (1322574-37-7)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In tetrahydrofuran; 1,2-dichloro-ethane at 20℃;	98%
With sodium tris(acetoxy)borohydride; acetic acid In tetrahydrofuran; 1,2-dichloro-ethane for 48h;

Cyclobutanecarboxylic acid (3721-95-7) + dehydroepiandrosterone (53-43-0) → 3β-cyclobutylcarbonyloxy-5-androsten-17-one (1345406-89-4)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 2h;	98%
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h;	90.4%
With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 2h;	84%
With dmap; dicyclohexyl-carbodiimide In chloroform Steglich Esterification;
With dmap; dicyclohexyl-carbodiimide

dehydroepiandrosterone (53-43-0) + 4-fluorobenzaldehyde (459-57-4) → (E)-16-(4-fluorophenyl)methylidene-trans-dehydroandrosterone (1428382-54-0)

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 1h;	98%
With potassium fluoride on basic alumina In ethanol for 1h; Claisen-Schmidt Condensation; Reflux;

dehydroepiandrosterone (53-43-0) + 2-methylphenyl aldehyde (529-20-4) → (E)-16-(2-methylphenyl)methylidene-trans-dehydroandrosterone (1428382-57-3)

Conditions	Yield
With potassium hydroxide In ethanol at 20℃; for 1h;	98%

dehydroepiandrosterone (53-43-0) + toluene-4-sulfonic acid hydrazide (1576-35-8) → dehydroepiandrosterone-17-p-toluenesulfonyl hydrazone (34988-34-6)

Conditions	Yield
With toluene-4-sulfonic acid In tetrahydrofuran Inert atmosphere; Reflux;	98%
With toluene-4-sulfonic acid In tetrahydrofuran Reflux; Inert atmosphere;	98%
With toluene-4-sulfonic acid In tetrahydrofuran for 3h; Inert atmosphere;	98%
With sulfuric acid In methanol for 5h; Reflux;	91.6%
With sulfuric acid In methanol at 15℃; for 2h; Concentration; Reflux;	81.4%

dehydroepiandrosterone (53-43-0) + 1-(3,4-dichlorophenyl)-1H-1,2,3-triazole-4-carbaldehyde (1325724-92-2) → (E)-16-((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methylene)-3-hydroxy-10,13-dimethyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14H)-one

Conditions	Yield
With potassium hydroxide In ethanol for 1h; Reflux;	98%

dehydroepiandrosterone (53-43-0) + 1-(2-bromophenyl)-4,5-dihydro-1H-1,2,3-triazole-4-carbaldehyde → (E)-16-((1-(2-bromophenyl)-1H-1,2,3-triazol-4-yl)methylene)-3-hydroxy-10,13-dimethyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14H)-one

Conditions	Yield
With potassium hydroxide In ethanol for 1h; Reflux;	98%

dehydroepiandrosterone (53-43-0) + C9H6BrN3O → (E)-16-((1-(3-bromophenyl)-1H-1,2,3-triazol-4-yl)methylene)-3-hydroxy-10,13-dimethyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14H)-one

Conditions	Yield
With potassium hydroxide In ethanol for 1h; Reflux;	98%

dehydroepiandrosterone (53-43-0) + 1-(2-fluorophenyl)-4,5-dihydro-1H-1,2,3-triazole-4-carbaldehyde → (E)-16-((1-(2-fluorophenyl)-1H-1,2,3-triazol-4-yl)methylene)-3-hydroxy-10,13-dimethyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14H)-one

Conditions	Yield
With potassium hydroxide In ethanol for 1h; Reflux;	98%

dehydroepiandrosterone (53-43-0) + 1-(3-fluorophenyl)-4,5-dihydro-1H-1,2,3-triazole-4-carbaldehyde → (E)-16-((1-(3-fluorophenyl)-1H-1,2,3-triazol-4-yl)methylene)-3-hydroxy-10,13-dimethyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14H)-one

Conditions	Yield
With potassium hydroxide In ethanol for 1h; Reflux;	98%

Upstream product

• 57-88-5 cholesterol 
• 83-46-5 β-sitosterol 
• 651-48-9 dehydroepiandrosterone sulfate 
• 571-36-8 5-androstenedione 
• 83205-52-1 3β-benzoyloxy-androst-5-en-17-one 
• 4350-66-7 17β-Aminoandrost-5-en-3β-ol 
• 35060-03-8 3β,17-dihydroxy-androst-5-ene-17α-carbonitrile 
• 60446-55-1 3β-acetoxy-20-methyl-pregnadiene-(5,17(20)) 
• 663-39-8 6β-hydroxy-3α,5-cycloandrostan-17-one 
• 897-01-8 (3S,8R,9S,10R,13S,14S)-3-Chloro-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-cyclopenta[a]phenanthren-17-one 
• 1857-79-0 5α,6β-dichlorocholestan-3β-ol 
• 1256-32-2 3β-acetoxy-5α-chloro-cholestane 
• 4651-48-3 acetic acid stigmasteryl ester 
• 514-50-1 3β-acetoxy-5α,6β-dibromocholestane 

Downstream Products

• 5419-51-2 3β-(2-tetrahydropyranyloxy)-5-androstene-17β-0l 
• 566-19-8 3β-hydroxyandrost-5-ene-7,17-dione 
• 628-13-7 pyridine hydrochloride 
• 521-17-5 androst-5-ene-3β,17β-diol 
• 63015-10-1 3β-Hydroxy-17-hydrazono-androsten-(5) 
• 853-23-6 3β-acetoxy-5-androsten-17-one 
• 1093-91-0 3β-Hydroxy-16α-brom-androst-5-en-17-on 
• 571-36-8 3,17-Dioxo-androsten-5 
• 521-17-5 5-androstenediol 
• 1963-03-7 androst-5-ene-3β,17α-diol 
• 65981-96-6 17βH-pregn-5-ene-3β,17-diol 
• 521-10-8 methylandrostenediol 
• 3091-03-0 17α-hydroxy-17β-methylandrost-5-en-3β-ol 
• 651-48-9 dehydroepiandrosterone sulfate 

Relevant articles and documents

Synthesis and structure determination of 3β-hydroxyandrost-5-en-17-one (C19H28O2·CH3OH)

3β-Hydroxyandrost-5-en-17-one (C19H28O 2.CH3OH) has been prepared for undertaking its crystallographic analysis and to investigate the role of intra- and intermolecular interactions in steroids. The title compound crystallizes in the orthorhombic space group C2221 with unit cell parameters a = 6.7892(17), b = 12.624(2), and c = 41.136(5) A; V = 3525.7(12) A3 and Z = 8. The three-dimensional structure has been solved by direct methods. The final reliability index for the computed structure is 0.050 for 1088 observed reflections. Ring A exist in chair conformation, Ring B in half-chair conformation, and the Ring C assumes a distorted chair conformation. The five-membered Ring D adopts half-chair conformation. The A/B ring junction is quasi-trans while as B/C and C/D are trans-fused. The oxygen atom of the solvent molecule (CH3OH) is involved in O-H···O intermolecular interaction.

A steroidogenic pathway for sulfonated steroids: The metabolism of pregnenolone sulfate

In many tissues sulfonated steroids exceed the concentration of free steroids and recently they were also shown to fulfill important physiological functions. While it was previously demonstrated that cholesterol sulfate (CS) is converted by CYP11A1 to pregnenolone sulfate (PregS), further conversion of PregS has not been studied in detail. To investigate whether a steroidogenic pathway for sulfonated steroids exists similar to the one described for free steroids, we examined the interaction of PregS with CYP17A1 in a reconstituted in-vitro system. Difference spectroscopy revealed a Kd-value of 74.8 ± 4.2 μM for the CYP17A1-PregS complex, which is 2.5-fold higher compared to the CYP17A1-pregnenolone (Preg) complex. Mass spectrometry experiments proved for the first time that PregS is hydroxylated by CYP17A1 at position C17, identically to pregnenolone. A higher Km- and a lower kcat-value for CYP17A1 using PregS compared with Preg were observed, indicating a 40% reduced catalytic efficiency when using the sulfonated steroid. Furthermore, we analyzed whether the presence of cytochrome b5(b5) has an influence on the CYP17A1 dependent conversion of PregS, as was demonstrated for Preg. Interestingly, with 17OH-PregS no scission of the 17,20-carbon-carbon bond occurs, when b5is added to the reconstituted in-vitro system, while b5promotes the formation of DHEA from 17OH-Preg. When using human SOAT-HEK293 cells expressing CYP17A1 and CPR, we could confirm that PregS is metabolized to 17OH-PregS, strengthening the potential physiological meaning of a pathway for sulfonated steroids.

Etherification of Hydroxystereoids via Triflates

Triflates of saturated alcohols are useful in the alkylation of 3- and 17-hydroxysteroids in the presence of hindered amines.The etherification is successful even in those cases where other alkylating agents are noneffective.

Modified bile acids and androstanes—Novel promising inhibitors of human cytochrome P450 17A1

Cytochromes P450 are key enzymes for steroid hormone biosynthesis in human body. They are considered as targets for the screening of novel high efficient drugs. The results of screening of bile acids and androstane derivatives toward human recombinant steroid 17α-hydroxylase/17,20-lyase (CYP17A1) are presented in this paper. A group of steroids, binding with micromolar or submicromolar affinity (in a range from 9 μM – less than 0.1 μM), was identified. Results presented here showed that these steroidal compounds are able to decrease rate of hydroxylation of essential CYP17A1 substrate – progesterone, while some compounds completely inhibited enzyme activity. Structure-activity relationship (SAR) analysis based on in vitro and in silico studies showed that high affinity of the enzyme to bile acids derivatives is correlated with side chain hydrophobicity and presence of hydroxyl or keto group at C3 position. From the other side, bile acid-derived compounds with more polar side chain or substituents at C7 and C12 positions possess higher Kd values. Among androstane-derived steroids couple of Δ5-steroids with hydroxyl group at C3 position, as well as 16,17-secosteroids, were found to be high affinity ligands of this enzyme. The data obtained could be useful for the design of novel highly efficient inhibitors of CYP17A1, since the bile acids-derived compounds are for first time recognized as effective CYP17A1 inhibitors.

Deconstructive Oxygenation of Unstrained Cycloalkanamines

A deconstructive oxygenation of unstrained primary cycloalkanamines has been developed for the first time using an auto-oxidative aromatization promoted C(sp3)?C(sp3) bond cleavage strategy. This metal-free method involves the substitution reaction of cycloalkanamines with hydrazonyl chlorides and subsequent auto-oxidative annulation to in situ generate pre-aromatics, followed by N-radical-promoted ring-opening and further oxygenation by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and m-cholorperoxybenzoic acid (mCPBA). Consequently, a series of 1,2,4-triazole-containing acyclic carbonyl compounds were efficiently produced. This protocol features a one-pot operation, mild reaction conditions, high regioselectivity and ring-opening efficiency, broad substrate scope, and is compatible with alkaloids, osamines, and peptides, as well as steroids.

Comprehensive kinetic and substrate specificity analysis of an arylsulfatase from Helix pomatia using mass spectrometry

Sulfatases hydrolyze sulfated metabolites to their corresponding alcohols and are present in all domains of life. These enzymes have found major application in metabolic investigation of drugs, doping control analysis and recently in metabolomics. Interest in sulfatases has increased due to a link between metabolic processes involving sulfated metabolites and pathophysiological conditions in humans. Herein, we present the first comprehensive substrate specificity and kinetic analysis of the most commonly used arylsulfatase extracted from the snail Helix pomatia. In the past, this enzyme has been used in the form of a crude mixture of enzymes, however, recently we have purified this sulfatase for a new application in metabolomics-driven discovery of sulfated metabolites. To evaluate the substrate specificity of this promiscuous sulfatase, we have synthesized a series of new sulfated metabolites of diverse structure and employed a mass spectrometric assay for kinetic substrate hydrolysis evaluation. Our analysis of the purified enzyme revealed that the sulfatase has a strong preference for metabolites with a bi- or tricyclic aromatic scaffold and to a lesser extent for monocyclic aromatic phenols. This metabolite library and mass spectrometric method can be applied for the characterization of other sulfatases from humans and gut microbiota to investigate their involvement in disease development.

Method for preparing 4-androstenedione from dehydroepiandrosterone acetate

The invention provides a method for preparing 4-androstenedione from dehydroepiandrosterone acetate. The method comprises the following steps: carrying out a hydrolysis reaction on dehydroepiandrosterone acetate to obtain dehydroepiandrosterone, carrying out an oxidation reaction on the dehydroepiandrosterone to obtain crude 4-androstenedione, adding methanol and dichloroethane to the crude 4-androstenedione, and performing purification to obtain refined 4-androstenedione, wherein the obtained refined 4-androstenedione can be further reacted with potassium tert-butoxide to obtain 5-androstenedione. The method for preparing 4-androstenedione from dehydroepiandrosterone acetate has the following advantages: the preparation process is simple and feasible, and the production rate is improved,so the production values of enterprises are improved; and the cheap dehydroepiandrosterone acetate is used as the raw material to prepare the 4-androstenedione greatly demanded on the market, and the4-androstenedione is reacted to further prepare the 5-androstenedione, so the production cost of the enterprise is saved.

Synthesis of 3β-methyl ether of dehydroepiandrosterone by biotransformation of 3β-methyl ether of cholesterol with cells of mycobacteria Mycobacterium sp.

3p-Methyl ether of dehydroepiandrosterone was obtained by microbiological transformation of 3?-methyl ether of cholesterol with Mycobacterium sp. Androstane-3,17-dione, androst-4-ene-3,17-dione, and androsta-1,4-diene-3,17-dione were minor transformation products.

Steroid compound 3-site hydroxyl configuration inversion method

The invention discloses a steroid compound 3-site hydroxyl configuration inversion method. The method specifically comprises the following steps that (1) a steroid compound containing a 3-site hydroxyl reacts with an acyl chloride compound; (2) the product obtained in the step (1) and a substituting agent are subjected to SN2 nucleophilic substitution reaction under existing of a phase transfer catalyst; and (3) the product obtained in the step (2) is subjected to a hydrolysis reaction. Compared with a Mitsunobu method, the method does not need to use triphenylphosphine and azodiformate pricedhigher, and accordingly the production cost is greatly lowered; meanwhile, a p-nitrobenzoic acid derivative which seriously affects the water environment does not need to be used, and therefore the method is more environmentally friendly. The method adopts cesium acetate/18-crown ether-6 system to conduct 3-site hydroxyl configuration inversion, can remarkably reduce occurrence of side reactions,accordingly a higher reaction yield is obtained, and the method is finally applicable to industrialized production.

STEROIDAL COMPOUND, COMPOSITION CONTAINING THE SAME AND USE THEREOF

Provided in the present invention are a steroidal compound, a composition containing the same and a use thereof. Specifically, disclosed in the present invention are a steroidal compound as shown in formula (I) and a drug composition containing the same, or a crystal form, a pharmaceutically acceptable salt, a hydrate or solvate, a stereoisomer, a prodrug, a metabolite or an isotopic variant thereof. The compound according to the present invention can be used as a CYP17 enzyme inhibitor, and has better pharmacokinetic parameters, which can improve drug concentration of the compound in an animal, thereby improving the efficacy and safety of the drug, and in turn the compound may be applied in the preparation of the drug for treating CYP17 enzyme-related diseases (such as prostate cancer).