58-18-4

Basic information

• Product Name: 17-Methyltestosterone
• Synonyms: METANDREN;MESTERONE;METHYLTESTOSTERONE;4-ANDROSTEN-17ALPHA-METHYL-17BETA-OL-3-ONE;17ALPHA-METHYLTESTOSTERONE;17ALPHA-METHYL-4-ANDROSTEN-17BETA-OL-3-ONE;17-METHYLTESTOSTERONE;17BETA-HYDROXY-17ALPHA-METHYL-4-ANDROSTEN-3-ONE
• CAS NO: 58-18-4
• Molecular Formula: C₂₀H₃₀O₂
• Molecular Weight: 302.45
• EINECS: 200-366-3
• Product Categories: Steroids;API's;Intermediates & Fine Chemicals;Pharmaceuticals;Steroid and Hormone;API;testosterone;Hormone Drugs;Inhibitors
• Mol File: 58-18-4.mol
• Article Data: 14

Chemical Properties

• Melting Point: 162-168 °C(lit.)
• Boiling Point: 383.47°C (rough estimate)
• Flash Point: 5 °C
• Appearance: white/solid (photosensitive)
• Density: 1.0434 (rough estimate)
• Vapor Pressure: 2.28E-09mmHg at 25°C
• Refractive Index: 1.4800 (estimate)
• Storage Temp.: 2-8°C
• Solubility: H2O: ≤0.5 mg/mL
• PKA: 15.13±0.60(Predicted)
• Water Solubility: 33.88mg/L(25 oC)
• Merck: 13,6148
• BRN: 2057425
• CAS DataBase Reference: 17-Methyltestosterone(CAS DataBase Reference)
• NIST Chemistry Reference: 17-Methyltestosterone(58-18-4)
• EPA Substance Registry System: 17-Methyltestosterone(58-18-4)

Safety Data

• Hazard Codes: T,Xn,F,Xi
• Statements: 45-63-22-20-19-11-61-60-36/37/38-38-10
• Safety Statements: 53-36/37-45-24/25-22
• RIDADR: 3249
• WGK Germany: 3
• RTECS: BV8400000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 58-18-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
17-Methyltestosterone is used as an androgenic agent for the treatment of sexual underdevelopment, functional problems of the reproductive system, and vascular nerve disorders associated with climacteric problems in men.
Used in Controlled Substances:
As an anabolic steroid, 17-Methyltestosterone is classified as a controlled substance due to its potential for abuse and side effects.
Used in Gynecological Applications:
17-Methyltestosterone is used for dysfunctional uterine bleeding in premenopausal and menopausal women, as well as for the treatment of breast and ovarian cancer.

Indication and administration

It has been used in the treatment of various symptoms such as hypogonadism, cryptorchidism, delayed puberty, and erectile dysfunction in males, and in low doses to treat menopausal symptoms (specifically for osteoporosis, hot flashes, and to increase libido and energy), postpartum breast pain and engorgement. In US, 17-Methyltestosterone is an anabolic steroid hormone that majorly used to treat men with a testosterone deficiency, hypogonadism and delayed puberty. Hypogonadism include both primary type and hypogonadotropic type: the former one can be caused by cryptorchidism, bilateral torsions, orchitis, vanishing testis syndrome; or orchidectomy. The later one includes idiopathic gonadotropin or LHRH deficiency, or pituitary hypothalamic injury from tumors, trauma, or radiation. It is also used in women to treat breast cancer, breast pain, swelling due to pregnancy, and with the addition of estrogen it can treat symptoms of menopause. It has also been used in combination with esterified estrogens for the treatment of moderate to severe vasomotor symptoms associated with menopause in females. 17-Methyltestosterone is administered orally. The suggested dosage varies depending on the age, sex, and diagnosis of the individual patient. Dosage is adjusted according to the patient's response and the appearance of adverse reactions. Replacement therapy in androgen-deficient males usually demands 10 to 50 mg of 17-Methyltestosterone daily. However, the chronological and skeletal ages must be taken into consideration both in determining the initial dose and in adjusting the dose. Doses used in the treatment of the delayed puberty generally are in the lower range of that given above, and for a limited duration, for example 4 to 6 months. For the treatment of women breast cancer, the dosage of 17-Methyltestosterone in females is from 50-200 mg daily.

Mode of action

17-Methyltestosterone take effects through two main mechanisms: activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. 17-Methyltestosterone can enter into the target tissue cells, binding to the androgen receptor, or being reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly, yielding a even stronger androgenic potency. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA, which is called hormone response elements (HREs). This process regulates the transcriptional activity of various genes, further producing the androgen effects.

Adverse reactions

17-methyltestosterone can cause various kinds of adverse reactions. Common side effects include increased facial/body hair growth, scalp hair loss, increased aggressiveness, skin, acne, seborrhea, and sex drive and spontaneous erections. There are also some kinds of estrogenic side effects such as breast tenderness, gynecomastia, fluid retention, and edema. Men can suffer hypogonadism, testicular atrophy, and reversible infertility. Women can sometimes suffer partially irreversible virilization including clitoromegaly, breast atrophy, voice deepening, hirsutism and muscle hypertrophy, as well as menstrual disturbances and reversible infertility. 17-methyltestosterone may also cause hepatotoxicity including elevated liver enzymes, cholestatic jaundice, peliosis hepatis, hepatomas, and hepatocellular carcinoma. It can also have adverse effect on the cardiovascular system such as causing erythropoiesis, increase hematocrit levels or even polycythemia, further leading to even thrombic events such as embolism and stroke. Finally, long-term treatment increase the risk of cancer. Some extreme cases also include hypomania/mania, depression, delusions, suicidality and psychosis.

Warning and precaution

People of the following cases should not use it: allergy; prostate cancer; male breast cancer, pregnant. People with liver or kidney disease, an enlarged prostate, heart disease, congestive heart failure should use with caution.

References

Alexandre Hohl (6 April 2017). Testosterone: From Basic to Clinical Aspects. Springer. pp. 204–. ISBN 978-3-319-46086-4. Shahidi NT (2001). "A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids". Clin Ther. 23 (9): 1355–90. Shi, Y., et al. "Molecular identification of an androgen receptor and its changes in mRNA levels during 17α-methyltestosterone-induced sex reversal in the orange-spotted grouper Epinephelus coioides. " Comp Biochem Physiol B Biochem Mol Biol 163.1(2012):43-50. Zheng, Z., B. A. Armfield, and M. J. Cohn. "Timing of androgen receptor disruption and estrogen exposure underlies a spectrum of congenital penile anomalies." PNAS 112.52(2015):201515981. Komada, S., et al. "Side gland of Suncus murinus, as a new model of sebaceous gland: 5α-reductase, androgen receptor, and nuclear androgen content in male and female animals." Archives of Dermatological Research 280.8(1989):487-493. Kicman, A T (2008). "Pharmacology of anabolic steroids". British Journal of Pharmacology. 154 (3): 502–521. Jeffrey K. Aronson (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 141–. ISBN 978-0-08-093292-7. Benjamin J. Sadock; Virginia A. Sadock (26 December 2011). Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. Lippincott Williams & Wilkins. ISBN 978-1-4511-7861-6. Bird, D. R., and K. D. Vowles. "Liver damage from long-term methyltestosterone. " Inpharma 310.8032(1977):261-263.

Originator

Metandren ,Ciba,US,1941

Manufacturing Process

0.6 g of 17-Methyl-?5,6-androstenediol-(3,17) is heated under reflux cooling during 20 hours in 50 cm3 of benzene and 12 cm3 of acetone with 3 g of tertiary chloromagnesium butylate, which may be prepared by conversion of acetone with methyl magnesium chloride. The magnesium is then removed by shaking out with dilute H2SO4; the benzene layer is washed with water, dried with sodium sulfate and then evaporated to dryness. Methyltestosterone (MP 160° to 162°C) is obtained in a yield of more than 75% of the theory, according to US Patent 2,384,335.

Therapeutic Function

Androgen

Pharmacokinetics

The synthesis of 17α-methyltestosterone made available a compound that was orally active in daily doses between 10 and 50 mg, which is equivalent to a 400 mg oral dose of testosterone. The presence of a 17α alkyl group reduces susceptibility to hepatic oxidative metabolism, thereby increasing oral bioavailability by slowing metabolism. Following oral administration, methyltestosterone is well absorbed from the gastrointestinal tract, with a half-life of approximately 3 hours. This drug has the androgenic and anabolic activities of testosterone. Although orally active, it is more effective when administered sublingually. The alkylated oral androgens should be viewed as potentially hepatotoxic and should not be used.

Safety Profile

Poison by intraperitoneal route. Moderately toxic by ingestion. Human teratogenic effects by ingestion: developmental abnormalities of the urogenital system. Experimental teratogenic and reproductive effects. Human systemic effects: cholestatic jaundce, weight loss or decreased weight gain. Questionable human carcinogen producing liver tumors. A synthetic androgenic steroid. When heated to decomposition it emits acrid smoke and irritating fumes.

Synthesis

Methyltestosterone, 17β-hydroxy-17α-methylandrost-4-en-3-one (29.1.7), is also synthesized from androstenolone by reacting it with methylmagnesiumiodide, forming the corresponding tertiary alcohol (29.1.6), and subsequent oxidation of the hydroxyl group at C3 to a ketone using chromium (VI) oxide. Simultaneous isomerization of the double bond takes place under the reaction conditions, giving the desired methyltestosterone (29.1.7).

Purification Methods

This anabolic steroid is crystallised from hexane or hexane/*benzene. It has E1cm 1% 495-530 at 241nm (EtOH). The colour reaction with 2,4-dinitrophenyl hydrazine is used for assaying it. [Gornall & Macdonald J Biol Chem 201 279 1953.] In another colour reaction the sterone (1mg) in acetic acid (0.2ml) + 88% H3PO4 (2mL) is allowed to stand for 1hour when it becames fluorescent. After 1hour it is diluted with acetic acid (~3mL) and provides a strong yellow fluorescence with the intensity of 50-100 times that of estrone. [Stuart & Stuckey J Pharm Pharmacol 1 130 1949, Openauer Rec Trav Chim Pays-Bas 56 137 137, Beilstein 8 IV 1010.]

InChI:InChI=1/C20H30O2/c1-18-9-6-14(21)12-13(18)4-5-15-16(18)7-10-19(2)17(15)8-11-20(19,3)22/h12,15-17,22H,4-11H2,1-3H3/t15-,16+,17+,18+,19+,20+/m1/s1

Synthetic route

(8R,9S,10R,13S,14S,17S)-10,13,17-Trimethyl-17-(tetrahydro-furan-2-yloxy)-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one (111222-36-7) → 17-methyltestosterone (58-18-4)

Conditions	Yield
With toluene-4-sulfonic acid In ethanol for 1h; Ambient temperature;	100%

methylandrostenediol (521-10-8) → 17-methyltestosterone (58-18-4)

Conditions	Yield
With <(C4Ph4COHOCC4Ph4)(μ-H)><(CO)4Ru2>; acetone at 56℃; for 18h;	93%
With chromium(VI) oxide; bromine; acetic acid Behandeln des Reaktionsprodukts mit CrCl2 in wss.Methanol unter Kohlendioxyd;
With aluminum tri-tert-butoxide; acetone; benzene

C22H34O2 → 17-methyltestosterone (58-18-4)

Conditions	Yield
With hydrogenchloride In water; toluene at 60 - 65℃; Solvent; Reagent/catalyst;	81.6%

ZINC05223451 (641-82-7, 641-84-9, 4085-03-4, 63088-07-3, 63121-01-7, 88729-24-2, 88729-25-3, 88729-26-4, 88729-27-5, 88980-24-9, 103881-21-6, 120925-80-6, 641-83-8) → 17-methyltestosterone (58-18-4) + 5α-17β-hydroxy-17α-methyl-Δ1-androsten-3-one (18167-94-7, 35937-38-3, 132830-76-3, 65-04-3)

Conditions	Yield
With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide at 65℃; for 24h;	A 10% B 74%
With 1-n-butyl-3-methylimidazolim bromide; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione at 65℃; for 22h;	A 10% B 74%

metandienone (72-63-9) → 17-methyltestosterone (58-18-4)

Conditions	Yield
With thallium(III) nitrate trihydrate In diethylene glycol dimethyl ether for 24h; Ambient temperature;	34%

pyridine (110-86-1) + methylandrostenediol (521-10-8) + trityl chloride (76-83-5) → 17-methyltestosterone (58-18-4)

Conditions	Yield
Erhitzen des Reaktionsprodukts mit Kupfer-Spaenen unter vermindertem Druck auf 250-300grad;

3-ethoxyandrosta-3,5-dien-17-one (972-46-3) + methylmagnesium bromide (75-16-1) → 17-methyltestosterone (58-18-4)

Conditions	Yield
With diethyl ether; toluene anschliessend Behandeln mit wss.NH4Cl und Behandeln des Reaktionsprodukts mit wss.Saeure;

methylandrostenediol (521-10-8) + cyclohexanone (108-94-1) → 17-methyltestosterone (58-18-4)

Conditions	Yield
With aluminum isopropoxide; toluene

methylandrostenediol (521-10-8) + cyclohexanone (108-94-1) + aluminum isopropoxide (555-31-7) + toluene (108-88-3) → 17-methyltestosterone (58-18-4)

methylandrostenediol (521-10-8) + trityl chloride (76-83-5) → 17-methyltestosterone (58-18-4)

Conditions	Yield
With pyridine Erhitzen des Reaktionsprodukts mit Kupfer-Spaenen unter vermindertem Druck auf 250-300grad;
With pyridine Erhitzen des Reaktionsprodukts mit Kupfer-Spaenen unter vermindertem Druck auf 250-300grad;

methylandrostenediol (521-10-8) + aluminum isopropoxide (555-31-7) + acetone (67-64-1) + benzene (71-43-2) → 17-methyltestosterone (58-18-4)

methylandrostenediol (521-10-8) + aluminum tri-tert-butoxide (556-91-2) + acetone (67-64-1) + benzene (71-43-2) → 17-methyltestosterone (58-18-4)

methylmagnesium bromide (75-16-1) + 3.3-ethylenedioxy-androsten-(4)-one-(17) → 17-methyltestosterone (58-18-4)

Conditions	Yield
With diethyl ether; toluene anschliessend mit wss.NH4Cl und Behandeln des Reaktionsprodukts mit wss.Saeure;

methylandrostenediol (521-10-8) + bromine (7726-95-6) + acetic acid (64-19-7) + CrO3 → 17-methyltestosterone (58-18-4)

Conditions	Yield
Behandeln des Reaktionsprodukts mit wss.-methanol. CrCl2-Loesung unter Kohlendioxyd;
Behandeln des Reaktionsprodukts in Aethanol und Benzol oder in Eisessig mit Zink-Pulver;
Behandeln des Reaktionsprodukts in Aethanol und Benzol oder in Eisessig mit Zink-Pulver;

methylandrostenediol (521-10-8) + acetone (67-64-1) + benzene (71-43-2) + magnesium chloride tert-butylate → 17-methyltestosterone (58-18-4)

17β-hydroxy-17α-methylandrost-4-ene (5225-36-5) + acetic acid (64-19-7) + CrO3 → 17-methyltestosterone (58-18-4)

dehydroepiandrosterone (53-43-0) → 17-methyltestosterone (58-18-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether 2: bromine; acetic acid; CrO3 / Behandeln von Loesungen des Reaktionsprodukts in Aethanol und Benzol oder in Essigsaeure mit Zink-Pulver View Scheme
Multi-step reaction with 2 steps 1: diethyl ether 2: bromine; acetic acid; CrO3 / Behandeln des Reaktionsprodukts mit CrCl2 in wss.Methanol unter Kohlendioxyd View Scheme

Progesterone (57-83-0) → 16-dehydroprogesterone (1096-38-4) + 17-methyltestosterone (58-18-4) + Pregnenolone (145-13-1) + 21-Hydroxyprogesterone (64-85-7) + pregna-4,7-diene-3,20-dione (17398-60-6) + pregnane-3,6,20-trione (30802-24-5) + pregnane-3,20-dione (7350-00-7)

Conditions	Yield
With Hortaea werneckii B-763 at all growth phases In YNB growth medium; N,N-dimethyl-formamide at 28℃; for 24h; Enzymatic reaction;

Chlorodifluoromethane (75-45-6) + C22H36O3 → 17-methyltestosterone (58-18-4)

Conditions	Yield
Stage #1: Chlorodifluoromethane With iodine; triethylamine In tetrahydrofuran at 40 - 45℃; for 1h; Stage #2: C22H36O3 In tetrahydrofuran; toluene at 1 - 45℃; for 24h;	33.9 g

C23H33NO3 → 17-methyltestosterone (58-18-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine; trichlorophosphate / N,N-dimethyl-formamide 2: sodium hydroxide; sodium tetrahydroborate 3: manganese(IV) oxide View Scheme

chloroform (67-66-3) + 3,17-dihydroxy-5-androstene (14504-94-0) → 17-methyltestosterone (58-18-4)

Conditions	Yield
With manganese(IV) oxide

3-acetyloxypregna-5,16-diene-20-one (38521-84-5) → 17-methyltestosterone (58-18-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydroxylamine hydrochloride 2: pyridine; trichlorophosphate / N,N-dimethyl-formamide 3: sodium hydroxide; sodium tetrahydroborate 4: manganese(IV) oxide View Scheme

Androstenedione (63-05-8) → 17-methyltestosterone (58-18-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / ethanol / 20 - 25 °C 2.1: magnesium / tetrahydrofuran / 45 - 50 °C 2.2: 50 - 55 °C 3.1: hydrogenchloride / toluene; water / 60 - 65 °C View Scheme
Multi-step reaction with 3 steps 1.1: hydrogenchloride / ethanol / 20 - 25 °C 2.1: magnesium / diethyl ether / 35 - 40 °C 2.2: 50 - 55 °C 3.1: hydrogenchloride / toluene; water / 60 - 65 °C View Scheme

3-ethoxyandrosta-3,5-dien-17-one (972-46-3) → 17-methyltestosterone (58-18-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: magnesium / tetrahydrofuran / 45 - 50 °C 1.2: 50 - 55 °C 2.1: hydrogenchloride / toluene; water / 60 - 65 °C View Scheme

tetrahydrofuran (109-99-9) + 17-methyltestosterone (58-18-4) → (8R,9S,10R,13S,14S,17S)-10,13,17-Trimethyl-17-(tetrahydro-furan-2-yloxy)-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one (111222-36-7)

Conditions	Yield
With tetrachloromethane; manganese at 65℃; for 8h;	91%
With ceric triethylammonium nitrate In toluene at 100℃; for 8h;	40%

17-methyltestosterone (58-18-4) → 2,17beta-Dihydroxy-17-methylandrosta-1,4-dien-3-one (2304-17-8)

Conditions	Yield
With 18-crown-6 ether; potassium tert-butylate; oxygen In toluene at -25℃; for 4h;	91%

17-methyltestosterone (58-18-4) → 17β-hydroxy-17α-methyl-3,5-seco-4-nor-5-oxo-androstan-3-oic acid (2931-65-9)

Conditions	Yield
With ozone at -31 - -29℃; for 1.5h; Inert atmosphere;	87%
With acetic acid Ozonolyse;
With ruthenium(IV) oxide; sodium periodate In tetrachloromethane; water; acetone for 0.5h;	10.96 g

17-methyltestosterone (58-18-4) → (1R,8S,9S,10R,13S,14S,17S)-1,17-Dihydroxy-10,13,17-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-2-oxa-cyclopenta[a]phenanthren-3-one (138513-20-9) + (1S,8S,9S,10R,13S,14S,17S)-1,17-Dihydroxy-10,13,17-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-2-oxa-cyclopenta[a]phenanthren-3-one (110716-65-9)

Conditions	Yield
With crown ether; potassium tert-butylate; oxygen In toluene 1.) -25 deg C, 1.5-4 h, 2.) room temperature, 3 d; Title compound not separated from byproducts;	A n/a B 85%

17-methyltestosterone (58-18-4) + ethylene glycol (107-21-1) → 3,3-(ethylenedioxy)-17α-methyl-5-androsten-17β-ol (1099-72-5)

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 4.5h; Heating;	82%
With toluene-4-sulfonic acid; benzene
With boron trifluoride diethyl etherate; orthoformic acid triethyl ester In chloroform at 30 - 35℃; for 9h; Solvent;	22.3 g

17-methyltestosterone (58-18-4) → metandienone (72-63-9)

Conditions	Yield
With tert-butyldimethylsilyl chloride; 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,4-dioxane at 0 - 20℃; for 48h;	78%
With selenium(IV) oxide
mit Hilfe von Didymella lycopersici;

17-methyltestosterone (58-18-4) → 6-Ketomethyltestosterone (96992-13-1)

Conditions	Yield
With potassium hydroxide; tetrazolium blue In ethanol Heating;	73%
Multi-step reaction with 2 steps 1: mit Hilfe von Rhizopus nigricans 2: CrO3; acetic acid View Scheme

17-methyltestosterone (58-18-4) → 17,17-dimethyl-18-norandrosta-4,13(14)-dien-3-one (1971-59-1)

Conditions	Yield
With hydrogenchloride at 60℃; for 0.5h;	65%
With N-(2-chloro-1,1,2-trifluoroethyl)diethylamine In acetonitrile
With hydrogenchloride In methanol Heating;
With hydrogenchloride
With hydrogenchloride; acetic acid

17-methyltestosterone (58-18-4) → 15α-hydroxy-17α-methyltestosterone + 15α,17β-dihydroxy-17α-methyl-5α-androstan-3-one

Conditions	Yield
With Penicillium notatum KCH 904 In water; acetone at 27℃; for 312h; Enzymatic reaction;	A 65% B 31%

17-methyltestosterone (58-18-4) → androsta-3,5-dien-17β-ol, 17-methyl-

Conditions	Yield
Stage #1: 17-methyltestosterone With C19H26ClIrN3O(1+)*Cl(1-) In water; acetonitrile at 80℃; for 0.166667h; Green chemistry; Stage #2: With formic acid In water; acetonitrile at 80℃; for 2h; Green chemistry;	63%
(i) LiAlH4, THF, (ii) aq. HCl, acetone; Multistep reaction;

formaldehyde diethyl acetal (462-95-3) + 17-methyltestosterone (58-18-4) → 17β-hydroxy-17α-methyl-6-methyleneandrost-4-en-3-one (80126-38-1)

Conditions	Yield
With sodium acetate; trichlorophosphate In chloroform for 1h; Heating;	51%
With sodium acetate; trichlorophosphate In chloroform

17-methyltestosterone (58-18-4) + Propargylamine (2450-71-7) → 17α-methyl-17β-hydroxy-5-ene-androst-3-eno[3,4-b]pyridine + C23H33NO

Conditions	Yield
With copper(II) nitrate In ethanol for 12h; Heating;	A 47% B 6%

17-methyltestosterone (58-18-4) → 15α-hydroxy-17α-methyltestosterone + 11α,17β-Dihydroxy-17α-methylandrost-4-en-3-one (1807-02-9) + 7α,17β-dihydroxy-17-methyl-4-androsten-3-one (972-50-9)

Conditions	Yield
With D-glucose In water; acetone at 25℃; Reagent/catalyst; Microbiological reaction;	A 19% B 17% C 45%

17-methyltestosterone (58-18-4) → 15α-hydroxy-17α-methyltestosterone + 12β-hydroxy-17α-methyltestosterone + 11α,17β-Dihydroxy-17α-methylandrost-4-en-3-one (1807-02-9) + 6β,17β-dihydroxy-17α-methylandrost-4-en-3-one (13096-49-6) + 15β-hydroxy-17α-methyltestosterone + 7α,17β-dihydroxy-17-methyl-4-androsten-3-one (972-50-9)

Conditions	Yield
With D-glucose In water; acetone at 25℃; Reagent/catalyst; Microbiological reaction;	A 9% B 29% C 5% D 34% E 4% F 6%

17-methyltestosterone (58-18-4) → 15α-hydroxy-17α-methyltestosterone + 11α,17β-Dihydroxy-17α-methylandrost-4-en-3-one (1807-02-9) + 6β,17β-dihydroxy-17α-methylandrost-4-en-3-one (13096-49-6) + 14α-hydroxy-17α-methyltestosterone + 6β,14α-dihydroxy-17α-methyltestosterone + 9α-hydroxy-17α-methyltestosterone + 7α,17β-dihydroxy-17-methyl-4-androsten-3-one (972-50-9)

Conditions	Yield
With D-glucose In water; acetone at 25℃; Reagent/catalyst; Microbiological reaction;	A 31% B 20% C 7% D 7% E 4% F 5% G 16%

17-methyltestosterone (58-18-4) → 17-methyl-estra-1,3,5(10)-triene-3,17α-diol (302-76-1) + 6β,12β-dihydroxy-17α-methyltestosterone + 7β-hydroxy-17α-methyltestosterone + 6β,17β-dihydroxy-17α-methylandrost-4-en-3-one (13096-49-6) + 6β,17β-dihydroxy-17α-methyl-1,4-androstadien-3-one (33526-41-9)

Conditions	Yield
With Acremonium strictum PTCC 5282 strain at 25℃; for 144h; pH=6.5; Enzymatic reaction;	A 7.6% B 24.3% C 16.7% D 28.4% E 9.5%

17-methyltestosterone (58-18-4) → 6β,17β-dihydroxy-17α-methylandrost-4-en-3-one (13096-49-6) + 6β,11α,17β-trihydroxy-17α-methylandrost-4-en-3-one

Conditions	Yield
With fungus Cephalosporium aphidicola In ethanol for 120h; hydroxylation;	A 17% B 4%

17-methyltestosterone (58-18-4) + UDP-glucuronic acid (2616-64-0) → 17α-methyl-5β-androstane-3α-ol-17β-O-glucuronide + 17α-methyl-5α-androstane-17β-ol-3α-O-glucuronide + 17α-methyl-5β-androstane-17β-ol-3α-O-glucuronide

Conditions	Yield
With liver microsomes from Aroclor 1254-induced male Wistar rat In methanol; phosphate buffer at 37℃; pH=7.4;	A 14% B n/a C n/a

17-methyltestosterone (58-18-4) → 17-Methyl-13,17-seco-androst-4-en-3,17-dion

Conditions	Yield
With silica gel for 46h; Irradiation;	7.9%

17-methyltestosterone (58-18-4) → C40H58O3 + C40H58O3

Conditions	Yield
for 4h; Irradiation;	A 1% B 5%

pyrrolidine (123-75-1) + 17-methyltestosterone (58-18-4) → 17α-methyl-3-pyrrolidino-androsta-3,5-dien-17β-ol (95908-76-2)

Conditions	Yield
With benzene

isoniazid (54-85-3) + 17-methyltestosterone (58-18-4) → 17β-hydroxy-17α-methyl-androst-4-en-3-one-isonicotinoylhydrazone (6180-04-7)

17-methyltestosterone (58-18-4) → ZINC05223451 (641-82-7, 641-84-9, 4085-03-4, 63088-07-3, 63121-01-7, 88729-24-2, 88729-25-3, 88729-26-4, 88729-27-5, 88980-24-9, 103881-21-6, 120925-80-6, 641-83-8) + mestanolone (521-11-9)

Conditions	Yield
With tetrahydrofuran; ammonia; lithium

17-methyltestosterone (58-18-4) → 17-Methylene-4-androstene-3-one (846-45-7)

Conditions	Yield
With copper(II) sulfate at 135 - 150℃; under 0.01 Torr;

Upstream product

• 5225-36-5 17β-hydroxy-17α-methylandrost-4-ene 
• 64-19-7 acetic acid 
• 108-94-1 cyclohexanone 
• 846-45-7 17-Methylene-4-androstene-3-one 
• 145-13-1 Pregnenolone 
• 53-43-0 dehydroepiandrosterone 
• 3091-03-0 17α-hydroxy-17β-methylandrost-5-en-3β-ol 
• 143579-42-4 methyltestosterone 17β-sulfate pyridinium salt 
• 101123-01-7 Sulfuric acid mono-((8R,9S,10R,13S,14S,17S)-10,13,17-trimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl) ester 
• 35900-10-8 17,20-epoxy-21-nor-pregn-4-en-3-one 
• 972-46-3 3-ethoxyandrosta-3,5-dien-17-one 
• 63-05-8 Androstenedione 
• 38521-84-5 3-acetyloxypregna-5,16-diene-20-one 
• 67-66-3 chloroform 

Downstream Products

• 846-45-7 17-Methylene-4-androstene-3-one 
• 58-18-4 17α-hydroxy-17β-methylandrost-4-en-3-one 
• 88495-36-7 17α-hydroxy-17β-methyl-5β-androstan-3-one 
• 33526-41-9 6β,17β-dihydroxy-17α-methyl-1,4-androstadien-3-one 
• 72-63-9 metandienone 
• 521-11-9 mestanolone 
• 1807-02-9 11α,17β-Dihydroxy-17α-methylandrost-4-en-3-one 
• 13096-49-6 6β,17β-dihydroxy-17α-methylandrost-4-en-3-one 
• 972-50-9 7α,17β-dihydroxy-17-methyl-4-androsten-3-one 
• 302-76-1 17-methyl-estra-1,3,5(10)-triene-3,17α-diol 

Relevant articles and documents

Testosterone preparation method

Provided is a testosterone preparation method. The method uses androstenedione (also known as 4AD) as the raw material and comprises the following steps: A, synthesizing imidazoleethylamine which is to mix the 4AD and triethyl orthoformate with higher alcohol organic solution for acid catalysis to obtain 3beta Ethoxy-androsta 3,5-diene 17-ketone; B, synthesizing reducing substance, mixing the imidazoleethylamine with organic solution, adding metal borohydride to reduce the 17 ketone to 3beta Ethoxy-androsta 3,5-diene 17-alcohol; C, synthesizing testosterone, mixing the aforementioned reducing substance with organic solution, hydrolyzing with water, conducting post-treatment to acquire the testosterone crude which is mixed with low carbon alcohol to be decolored by active carbon and recrystallized, obtaining the final product of testosterone. The overall recovery rate of synthesized weight is 70%-75%. The method has the advantages of widely available material sources, simple operation, high yield rate, high purity, extreme reduction of costs, high recovery rate of solution in the reaction and processing, cost effectiveness and environmental protection.

Preparation method of methyltestosterone

The invention provides a preparation method of methyltestosterone. 4AD short for 4-androstenedione is taken as a raw material, and etherate is synthesized firstly as follows: 4AD and triethyl orthoformate are subjected to an acid catalyzed reaction in a low-carbon alcohol organic solvent, and 3-ethoxy-androst-3,5-diene-17-one as the etherate is obtained; then a Grignard product is synthesized as follows: a Grignard reagent methyl magnesium halide and the etherate are placed in an organic solvent, the 17-position ketone group of the etherate and the Grignard reagent are subjected to addition, and the Grignard product 3-ethoxy-17a-methyl-androst-3,5-diene-17-ol is obtained through hydrolysis; then the Grignard product is subjected to an acid catalyzed hydrolysis in an organic solvent, and crude methyltestosterone is obtained; the crude methyltestosterone is decolorized by activated carbon in C4-below low-carbon alcohol and recrystallized, the methyltestosterone is obtained, HPLC content is 99.0%-99.5%, and the total yield of synthesis weight is 75%-78%. According to the method, the raw materials are widely sourced, the process is simple and convenient to operate, the product yield is high, the purity is good, the solvent recovery rate is high in reaction and technological processing, and the method is economical and environment-friendly.

Preparation method for methyltestosterone

The invention provides a preparation method for methyltestosterone. According to the preparation method, methyltestosterone is prepared by taking androstenedione as a raw material and successively performing position-3 keto protection reaction, grignard addition reaction, position-3 keto deprotection and position-17 hydrolysis reaction. The technology possesses the characteristics of being high in reaction selectivity, high in operation safety, simple and easily-realizable for industrialization, low in production cost, high in yield, applicability to industrial large-scale production.

Aspects of the progesterone response in Hortaea werneckii: Steroid detoxification, protein induction and remodelling of the cell wall

Progesterone in sublethal concentrations temporarily inhibits growth of Hortaea werneckii. This study investigates some of the compensatory mechanisms which are activated in the presence of progesterone and are most probably contributing to escape from growth inhibition. These mechanisms lead on the one hand to progesterone biotransformation/detoxification but, on the other, are suggested to increase the resistance of H. werneckii to the steroid. Biotransformation can detoxify progesterone efficiently in the early logarithmic phase, with mostly inducible steroid transforming enzymes, while progesterone biotransformation/detoxification in the late logarithmic and stationary phases of growth is not very efficient. The relative contribution of constitutive steroid transforming enzymes to progesterone biotransformation is increased in these latter phases of growth. In the presence of progesterone, activation of the cell wall integrity pathway is suggested by the overexpression of Pck2 which was detected in the stationary as well as the logarithmic phase of growth of the yeast. Progesterone treated H. werneckii cells were found to be more resistant to cell lysis than mock treated cells, indicating for the first time changes in the yeast cell wall as a result of treatment with progesterone.

Synthesis and X-ray crystallographic analysis of 17α-hydroxy-17- methylandrost-4-ene-17-one

17α-Hydroxy-17-methylandrost-4-ene-17-one is a complex of two steroid molecules with water and its crystal structure has been determined by X-ray crystallographic techniques. The transparent plate-like crystals of this compound crystallized in the orthorhombic space group P212 121, with unit cell parameters: a = 6.382(2), b = 12.841(5), c = 43.350(2) A, λ(Mo Kα) = 0.71073 A, Z = 8. The structure has been solved by direct methods and refined to R = 0.047, wR = 0.086. There are two crystallographically independent molecules, I and II, in the asymmetric unit. In both the molecules, rings A and D adopt a distorted half-chair conformation while rings B and C exist in chair conformation. The crystal structure is stabilized by intermolecular O-H...O and C-H...O hydrogen bonds.

Efficient oxidizing methods for the synthesis of oxandrolone intermediates

Mild, efficient and eco-friendly oxidation of 17α-methylandrostan- 3β-17β-diol (1) has been studied with three different reagents viz. pentavalent iodine reagent 2-iodoxy benzoic acid (IBX) in DMSO at 65°C, sodium hypochlorite and H2O2/Na2WO4 under phase transfer conditions to give 17β-hydroxy-17α- methylandrostan-3-one (mestanolone 2), a drug intermediate as oxidized product. The H2O2/Na2WO4/PTC gave mestanolone in high yield and purity whereas sodium hypochlorite/PTC system yielded some chlorinated material along with the mestanolone. However, 1 with 2.5 equivalent of IBX gave 17β-hydroxy-17α-methyl- Δ1-androsten-3- one (3) under the similar reaction conditions in good yield and single step reaction.

IBX in an ionic liquid: Eco-friendly oxidation of 17α- methylandrostan-3β,17β-diol, an intermediate in the synthesis of anabolic oxandrolone

An easily available hypervalent iodine(V) reagent, 2-iodoxybenzoic acid (IBX) immobilized in the ionic liquid [bmim][Br] was found to be an efficient and eco-friendly protocol for the oxidation of 17α-methylandrostan- 3β,17β-diol (1). At ambient temperature oxidation of 1 with IBX gave mestanolone (2) in good yield and with an increased stoichiometric amount of IBX, oxidation adjacent to the carbonyl functionality (α,β- unsaturation) occurred to give dehydrogenated 17β-hydroxy-17α-methyl- Δ1-androsten-3-one (3) as the major product in a one-pot reaction. The product is easily obtained by extraction with diethyl ether and evaporation of the solvent.

Ruthenium-catalyzed Oppenauer-type oxidation of 3β-hydroxy steroids. A highly efficient entry into the steroidal hormones with 4-en-3-one functionality

Oxidation of 5-unsaturated 3β-hydroxy steroids 1 to the corresponding 4-en-3-one derivatives 2 can be performed efficiently by acetone at reflux in the presence of a catalytic system consisting of either (PPh3)3RuCl2 (3) and K2CO3 or [(C4Ph4COHOCC4Ph4)(μ-H)][(CO)4Ru2] (4). The reaction proceeds via a ruthenium-catalyzed dehydrogenation of 1 and subsequent hydrogen transfer to acetone with concomitant double bond migration.

17-Epimerization of 17α-methyl anabolic steroids in humans: metabolism and synthesis of 17α-hydroxy-17β-methyl steroids

The 17-epimers of the anabolic steroids bolasterone (I), 4-chlorodehydromethyltestosterone (II), fluoxymesterone (III), furazabol (IV), methanedienone (V), mestanolone (VI), methyltestosterone (VII), methandriol (VIII), oxandrolone (IX), oxymesterone (X), oxymetholone (XI), stanozolol (XII), and the human metabolites 7α,17α-dimethyl-5β-androstane-3α,17β-diol (XIII) (metabolite of I), 6β-hydroxymetandienone (XIV) (metabolite of V), 17α-methyl-5β-androst-1-ene-3α,17β-diol (XV) (metabolite of V), 3'-hydroxystanozolol (XVI) (metabolite of XII), as well as the reference substances 17β-hydroxy-17α-methyl-5β-androstan-3-one (XVII), 17β-hydroxy-17α-methyl-5β-androst-1-en-3-one (XVIII) (also a metabolite of V), the four isomers 17α-methyl-5α-androstane-3α,17β-diol (XIX) (also a metabolite of VI, VII, and XI), 17α-methyl-5α-androstane-3β,17β-diol (XX), 17α-methyl-5β-androstane-3α,17β-diol (XXI) (also a metabolite of V, VII, and VIII), 17α-methyl-5β-androstane-3β,17β-diol (XXII), and 17β-hydroxy-7α,17α-dimethyl-5β-androstan-3-one (XXIII) were synthesized via a 17β-sulfate that spontaneously hydrolyzed in water to several dehydration products, and to the 17α-hydroxy-17β-methyl epimer.The 17β-sulfate was prepared by reaction of the 17β-hydroxy-17α-methyl steroid with sulfur trioxide pyridine complex.The 17β-methyl epimers are eluted in gas chromatography as trimethylsilyl derivatives from a capillary SE-54 or OV-1 column 70-170 methylen units before the corresponding 17α-methyl epimer.The electron impact mass spectra of the underivatized and trimethylsilylated epimers are in most cases identical and only for I, II, and V was a differentiation between the 17-epimers possible. 1H nuclear magnetic resonance (NMR) spectra show for the 17β-methyl epimer a chemical shift for the C-18 protons (singlet) of about 0.175 ppm (in deuterochloroform) to a lower field. 13C NMR spectra display differences for the 17-epimeric steroids in shielding effects for carbons 12-18 and 20.Excretion studies with I-XII with identification and quantification of 17-epimeric metabolites indicate that the extent of 17-epimerization depends on the A-ring structure and shows a great variation for the different 17α-methyl anabolic steroids.Keywords: anabolic steroids; 17-epimerization; nuclear magnetic resonance; Kovats indices; mass spectrometry; metabolism; gas chromatography

Studies on anabolic steroids. 9. Tertiary sulfates of anabolic 17α-methyl steroids: synthesis and rearrangement

A simple and convenient method has been developed to prepare sulfates of anabolic 17β-hydroxy-17α-methyl steroids.The sulfates of methandienone, 17α-methyltestosterone, mestanolone, oxandrolone, and stanozolol were prepared.Different A-ring functions were not affected under the sulfation condition.The buffered hydrolyses of these sulfates provided the 17-epimers of the original steroids and 17,17-dimethyl-18-nor-13(14)-ene steroids, presumably via the 17-carbocations. Keywords: steroids, tertiary sulfates; 17α-methyl steroids; 17β-methyl steroids; 17,17-dimethyl-18-norandrost-13(14)-enes; NMR