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

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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]

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. ↑ "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): 1597–1599. April 1981. doi:10.1210/endo-108-4-1597. PMID 7472286. 
  2. ↑ "Sex steroids modulate changes in social and sexual preference during juvenile development in zebra finches". Hormones and Behavior (Elsevier Inc) 50 (5): 772–778. December 2006. doi:10.1016/j.yhbeh.2006.07.003. PMID 16919276. 
  3. ↑ "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): 207–218. January 2009. doi:10.1002/rcm.3861. PMID 19089863. Bibcode: 2009RCMS...23..207P. 
  4. ↑ Ma, E., Kim, E. (25 May 2005). "Epoxidation and Reduction of DHEA, 1,4,6-Androstatrien-3-one and 4,6-Androstadien-3β,17β-diol". Molecules. 10 (3): 572–582. 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): 360–367. 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 Wohl—Ziegler Bromination of Steroidal 1,4-Dien-3-ones. Partial Synthesis of ▵ 6 -Dehydroestrone and Equilenin". Journal of the American Chemical Society. 72 (10): 4531–4534. doi:10.1021/ja01166a054.
  9. ↑ Rubin Martin, Emanuel B Hershberg & Schwenk Erwin, US2594349 (1952 to Merck Sharp and Dohme LLC).
  10. ↑ 田伟生, 史勇 & 汪昀, 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).

Further reading

  • "Inhibition of aromatization stimulates luteinizing hormone and testosterone secretion in adult male rhesus monkeys". The Journal of Clinical Endocrinology and Metabolism 59 (6): 1088–1096. December 1984. doi:10.1210/jcem-59-6-1088. PMID 6541658. 



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