1,4,6-Androstatriene-3,17-dione

1,4,6-Androstatriene-3,17-dione (ATD) is a potent irreversible aromatase inhibitor that inhibits estrogen biosynthesis by permanently binding and inactivating aromatase in adipose and peripheral tissue.^[1] It is used to control estrogen synthesis.^[2]

Routes of
administrationOral

Legal status

US: Supplement

MetabolismHepatic

Elimination half-life48 hours

Quick facts Clinical data, Routes ofadministration ...

1,4,6-Androstatriene-3,17-dione
Clinical data

Routes of administration	Oral
Legal status
Legal status	US: Supplement
Pharmacokinetic data
Metabolism	Hepatic
Elimination half-life	48 hours
Identifiers
IUPAC name (8R,9S,10R,13S,14S)-10,13-dimethyl-9,11,12,14,15,16-hexahydro-8H-cyclopenta[a]phenanthrene-3,17-dione
CAS Number	633-35-2
PubChem CID	104880
ChemSpider	94659^Y
UNII	217A6T1V8N
ChEBI	CHEBI:131190^Y
CompTox Dashboard (EPA)	DTXSID60862328
Chemical and physical data
Formula	C₁₉H₂₂O₂
Molar mass	282.383 gÂ·mol^â1
3D model (JSmol)	Interactive image
SMILES O=C\4\C=C/[C@]3(C(/C=C\[C@H]2[C@H]1[C@@](C(=O)CC1)(CC[C@@H]23)C)=C/4)C
InChI InChI=1S/C19H22O2/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/h3-4,7,9,11,14-16H,5-6,8,10H2,1-2H3/t14-,15-,16-,18-,19-/m0/s1^Y Key:DKVSUQWCZQBWCP-QAGGRKNESA-N^Y
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ATD was present in some over-the-counter bodybuilding supplements until 2009, as well as Topical ATD solutions that work transdermally. The product was developed and commercialized in the dietary supplement market place by industry journeyman Bruce Kneller, who holds a United States Patent for use of the compound and related compounds (#7,939,517) and Gaspari Nutrition. ATD has many names in sports supplements including: 1,4,6 etiollochan-dione, 3, 17-keto-etiochol-triene, androst-1,4,6-triene-3,17-dione and many others. These all refer to CAS# 633-35-2.

ATD may cause a positive test for the anabolic steroid Boldenone, of which it is a possible metabolite and production contaminant. ATD is also prohibited in amateur and professional sports which forbids aromatase inhibitors.^[3]

A related agent is exemestane (Aromasin).

Synthesis

The synthesis of 1,4,6-Androstatriene-3,17-dione has been described:^[4]^[5]^[6]^[7]^[8] It is most congenially prepared from DHEA by oxidation with DDQ in a single step.

Applications

It is possible to use 1,4,6-Androstatriene-3,17-dione in the synthesis of estrone.^[9] However, the modern process seems to rely on Boldione.^[10]
1,4,6-Androstatriene-3,17-dione is used in the synthesis of 1-Methylestrone methyl ether, PC22295924.^[11] Birch reduction of this and work-up can lead to some interesting steroids with a 1-methyl group,^[12] although according to Dan the methyl group is in the beta-configuration.^[13] However, according to one patent, there is a scrambling of alpha/beta epimers and not a single isomer.^[14] Hence, this is the estrane equivalent of Demalon [2881-21-2] but a mixture of epimers.

References

[1]
Covey DF, Hood WF (April 1981). "Enzyme-generated intermediates derived from 4-androstene-3,6,17-trione and 1,4,6-androstatriene-3,17-dione cause a time-dependent decrease in human placental aromatase activity". Endocrinology. 108 (4): 1597â1599. doi:10.1210/endo-108-4-1597. PMID 7472286.
[2]
Adkins-Regan E, Leung CH (December 2006). "Sex steroids modulate changes in social and sexual preference during juvenile development in zebra finches". Hormones and Behavior. 50 (5). Elsevier Inc: 772â778. doi:10.1016/j.yhbeh.2006.07.003. PMID 16919276. S2CID 23869106.
[3]
Parr MK, FusshÃ¶ller G, SchlÃ¶rer N, Opfermann G, Piper T, Rodchenkov G, SchÃ¤nzer W (January 2009). "Metabolism of androsta-1,4,6-triene-3,17-dione and detection by gas chromatography/mass spectrometry in doping control". Rapid Communications in Mass Spectrometry. 23 (2): 207â218. Bibcode:2009RCMS...23..207P. doi:10.1002/rcm.3861. PMID 19089863.
[4]
Ma, E., Kim, E. (25 May 2005). "Epoxidation and Reduction of DHEA, 1,4,6-Androstatrien-3-one and 4,6-Androstadien-3Î²,17Î²-diol". Molecules. 10 (3): 572â582. doi:10.3390/10030572.
[5]
Kim, E., Ma, E. (April 2007). "Chemoselective reduction of 1,4,6-cholestatrien-3-one and 1,4,6-androstatriene-3,17-dione by various hydride reagents". Steroids. 72 (4): 360â367. doi:10.1016/j.steroids.2006.12.008.
[6]
Turner, A. B. (1966). "Applications of high-potential quinones. Convenient syntheses of steroidal 1,4,6-trien-3-ones". Chemical Communications (London) (23): 845. doi:10.1039/c19660000845.
[7]
Burg Willem Jacob Van Der, US2879279 (1959 to Organon NV, Organon Inc).
[8]
Kaufmann, St., Pataki, J., Rosenkranz, G., Romo, J., Djerassi, C. (October 1950). "Steroids. VI. 1 The WohlâZiegler Bromination of Steroidal 1,4-Dien-3-ones. Partial Synthesis of âµ 6 -Dehydroestrone and Equilenin". Journal of the American Chemical Society. 72 (10): 4531â4534. doi:10.1021/ja01166a054.
[9]
Rubin Martin, Emanuel B Hershberg & Schwenk Erwin, US2594349 (1952 to Merck Sharp and Dohme LLC).
[10]
ç°ä¼ç, å²å & æ±ªæ, CN107602650 (2018 to Shanghai Institute of Organic Chemistry of CAS).
[11]
S Laing & P Sykes, U.S. patent 3,717,627 (1973 to Glaxo Laboratories Ltd).
[12]
Howard J Ringold & Rosenkranz George, U.S. patent 3,032,552 (1962 to Syntex SA).
[13]
Lednicer, D. (2011). Steroid chemistry at a glance. Chemistry at a glance (1. publ ed.). Wiley. ISBN 978-0-470-66084-3.
[14]
David Darwin Evans, GB1003301 (1965 to Parke Davis and Co LLC).

1,4,6-Androstatriene-3,17-dione

Synthesis

Applications

References

Further reading

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