Bolandione
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| Other names | 19-Norandrostenedione; Estr-4-ene-3,17-dione; 19-Norandrost-4-en-3,17-dione |
| Routes of administration | By mouth |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.010.906 |
| Chemical and physical data | |
| Formula | C18H24O2 |
| Molar mass | 272.388 g·mol−1 |
| 3D model (JSmol) | |
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Bolandione, also known as 19-norandrostenedione, as well as 19-norandrost-4-en-3,17-dione or estr-4-ene-3,17-dione, is a precursor of the anabolic-androgenic steroid (AAS) nandrolone (19-nortestosterone). Until 2005, bolandione was available without prescription in United States, where it was marketed as a prohormone, but it is now classified as a Schedule III drug. It is also banned from use in many sports, including the Olympic Games, under the World Anti-Doping Code.[1] Bolandione is readily metabolized to nandrolone after oral administration, but its potency to transactivate the androgen receptor dependent reporter gene expression is 10 times lower as compared to dihydrotestosterone (DHT).[2]
Animal studies
Scientific studies have shown that oral administration of bolandione is "a very ineffective strategy for stimulating skeletal muscle mass increases but may be associated with side effects".[3]
In vivo experiments in castrated rats demonstrated that subcutaneous treatment with bolandione resulted only in a stimulation of the weight of the levator ani muscle, while the prostate and seminal vesicle weights remained completely unaffected. In contrast to its metabolite nandrolone, bolandione highly selectively stimulates the growth of the skeletal muscles but has only weak androgenic properties.[2]
Society and culture
In the early 2000s, contamination of androstenedione products with traces of bolandione caused false positives for doping tests for nandrolone because 19-norandrosterone is a metabolite of both nandrolone and bolandione. In a randomized controlled trial trace contamination of androstenedione with bolandione was sufficient for users of androstenedione to test positive for nandrolone.[4] This detail became less relevant after bolandione and 4-androstenedione were banned by major sporting bodies.
Synthesis and applications
In the total synthesis, bolandione is made by Birch reduction of estrone methyl ether to nandrolone and back-oxidation of the reduced 17-keto group.[5] Protecting the 17-position with ethylene glycol obviates the need for having to perform an oxidation step.[6]
The semi-synthesis uses sitolactone as the starting material.[7][8][9]
Bolandione finds use in the synthesis of norethandrolone,[10] norethindrone, and normethandrone. Bolandione finds use in the synthesis of 6-dehydronandrolone acetate,[11] a chemical with application in the synthesis of fulvestrant, tibolone, mibolerone, and isotibolone. A further use for bolandione is in the synthesis of 19-nordehydroepiandrosterone.[12] One further use of bolandione is in the synthesis of allylestrenol.[13] Bolandione finds use in the synthesis of Segesterone acetate.
See also
References
- ^ "The World Anti-Doping Code: The 2012 Prohibited List" (PDF). World Anti-Doping Agency. Archived from the original (PDF) on 2012-05-13. Retrieved 2012-07-16.
- ^ a b Diel P, Friedel A, Geyer H, Kamber M, Laudenbach-Leschowsky U, Schänzer W, et al. (April 2008). "The prohormone 19-norandrostenedione displays selective androgen receptor modulator (SARM) like properties after subcutaneous administration". Toxicology Letters. 177 (3): 198–204. doi:10.1016/j.toxlet.2008.01.014. PMID 18325697.
- ^ Parr MK, Laudenbach-Leschowsky U, Höfer N, Schänzer W, Diel P (July 2009). "Anabolic and androgenic activity of 19-norandrostenedione after oral and subcutaneous administration--analysis of side effects and metabolism". Toxicology Letters. 188 (2): 137–141. doi:10.1016/j.toxlet.2009.03.024. PMID 19446246.
- ^ Catlin DH, Leder BZ, Ahrens B, Starcevic B, Hatton CK, Green GA, Finkelstein JS (2000). "Trace contamination of over-the-counter androstenedione and positive urine test results for a nandrolone metabolite". JAMA. 284 (20): 2618–2621. doi:10.1001/jama.284.20.2618. PMID 11086369.
- ^ Krohn, K., Vinke, I., Adam, H. (1 January 1996). "Transition-Metal Catalyzed Oxidations. 7. Zirconium-Catalyzed Oxidation of Primary and Secondary Alcohols with Hydroperoxides". The Journal of Organic Chemistry. 61 (4): 1467–1472. doi:10.1021/jo9518720.
- ^ Czakó, B., Kürti, L., Mammoto, A., Ingber, D., Corey, E. (December 2009). "Synthesis of Cortistatin Analogues". Synfacts. 2009 (12): 1316–1316. doi:10.1055/s-0029-1218326.
- ^ 刘喜荣 & 曾春玲, CN104497088 (2015 to HUNAN XINHEXIN BIOLOGICAL PHARMACEUTICAL Co Ltd).
- ^ Joel Edward Kalamazoo Mich. Huber, DE3208432 (1983 to Pharmacia and Upjohn Co).
- ^ Joel E. Huber, U.S. patent 4,400,524 (1983 to Pharmacia and Upjohn Co).
- ^ Left Power, et al. CN115286672 (2022 to Huanggang Renfu Pharmaceutical Co ltd)
- ^ Zeng Chunling, et al. CN118290508 (2024 to Hunan Xinhexin Biological Medicine Co ltd).
- ^ Tang Sihua, et al. CN117820407 (2024 to Hubei Tongtong Steroidal Drug Research Institute Co ltd).
- ^ 郑正春, et al. CN102225960 (2012 to Beijing Keyifeng Biotech Development Co ltd).