# Bolandione

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Bolandione
> Markdown URL: https://mediated.wiki/source/Bolandione.md
> Source: https://en.wikipedia.org/wiki/Bolandione
> Source revision: 1341537173
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{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477209395
| IUPAC_name = (8''R'',9''S'',10''R'',13''S'',14''S'')-13-Methyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[''a'']phenanthrene-3,17-dione
| image = Bolandione.svg
| image_class = skin-invert-image
| width = 225px

<!--Clinical data-->
| tradename = 
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = Schedule III
| legal_status =
| routes_of_administration = [By mouth](/source/Oral_administration)

<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 734-32-7
| PubChem = 92834
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01434
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = U90987PVU5
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 83803
| synonyms = 19-Norandrostenedione; Estr-4-ene-3,17-dione; 19-Norandrost-4-en-3,17-dione

<!--Chemical data-->
| C=18 | H=24 | O=2 
| SMILES = O=C4/C=C3/CC[C@@H]2[C@H](CC[C@@]1(C(=O)CC[C@H]12)C)[C@H]3CC4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h10,13-16H,2-9H2,1H3/t13-,14+,15+,16-,18-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JRIZOGLBRPZBLQ-QXUSFIETSA-N
}}

'''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](/source/precursor_(chemistry)) of the [anabolic-androgenic steroid](/source/anabolic-androgenic_steroid) (AAS) [nandrolone](/source/nandrolone) (19-nortestosterone). Until 2005, bolandione was available without prescription in United States, where it was marketed as a [prohormone](/source/prohormone), but it is now classified as a [Schedule III](/source/Controlled_Substances_Act) drug. It is also banned from use in many sports, including the [Olympic Games](/source/Olympic_Games), under the [World Anti-Doping Code](/source/World_Anti-Doping_Code).<ref>{{cite web | url=http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/2012/WADA_Prohibited_List_2012_EN.pdf | title=The World Anti-Doping Code: The 2012 Prohibited List | publisher=[World Anti-Doping Agency](/source/World_Anti-Doping_Agency) | access-date=2012-07-16 | url-status=dead | archive-url=https://web.archive.org/web/20120513020202/http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/2012/WADA_Prohibited_List_2012_EN.pdf | archive-date=2012-05-13 }}</ref> Bolandione is readily metabolized to nandrolone after oral administration, but its potency to [transactivate](/source/transactivate) the [androgen receptor](/source/androgen_receptor) dependent reporter gene expression is 10 times lower as compared to [dihydrotestosterone](/source/dihydrotestosterone) (DHT).<ref name=sarm>{{cite journal | vauthors = Diel P, Friedel A, Geyer H, Kamber M, Laudenbach-Leschowsky U, Schänzer W, Schleipen B, Thevis M, Vollmer G, Zierau O | display-authors = 6 | title = The prohormone 19-norandrostenedione displays selective androgen receptor modulator (SARM) like properties after subcutaneous administration | journal = Toxicology Letters | volume = 177 | issue = 3 | pages = 198–204 | date = April 2008 | pmid = 18325697 | doi = 10.1016/j.toxlet.2008.01.014 }}</ref>

== 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".<ref>{{cite journal | vauthors = Parr MK, Laudenbach-Leschowsky U, Höfer N, Schänzer W, Diel P | title = Anabolic and androgenic activity of 19-norandrostenedione after oral and subcutaneous administration--analysis of side effects and metabolism | journal = Toxicology Letters | volume = 188 | issue = 2 | pages = 137–141 | date = July 2009 | pmid = 19446246 | doi = 10.1016/j.toxlet.2009.03.024 }}</ref>

''In vivo'' experiments in [castrated](/source/castrated) rats demonstrated that [subcutaneous](/source/Subcutaneous_injection) treatment with bolandione resulted only in a stimulation of the weight of the [levator ani](/source/levator_ani) muscle, while the [prostate](/source/prostate) and seminal vesicle weights remained completely unaffected. In contrast to its metabolite nandrolone, bolandione highly selectively stimulates the growth of the [skeletal muscle](/source/skeletal_muscle)s but has only weak [androgenic](/source/androgenic) properties.<ref name=sarm/>

== Society and culture ==

In the early 2000s, contamination of [androstenedione](/source/androstenedione) products with traces of bolandione caused false positives for [doping](/source/Doping_(sport)) tests for [nandrolone](/source/nandrolone) because [19-norandrosterone](/source/19-norandrosterone) is a metabolite of both [nandrolone](/source/nandrolone) and bolandione. In a [randomized controlled trial](/source/randomized_controlled_trial) trace contamination of androstenedione with bolandione was sufficient for users of androstenedione to test positive for nandrolone.<ref>{{cite journal | vauthors = Catlin DH, Leder BZ, Ahrens B, Starcevic B, Hatton CK, Green GA, Finkelstein JS | title = Trace contamination of over-the-counter androstenedione and positive urine test results for a nandrolone metabolite | journal = JAMA | volume = 284 | issue = 20 | pages = 2618–2621 | year = 2000 | pmid = 11086369 | doi = 10.1001/jama.284.20.2618 | doi-access = free }}</ref> This detail became less relevant after bolandione and 4-androstenedione were banned by major sporting bodies.
==Synthesis and applications==
In the [total synthesis](/source/total_synthesis), bolandione is made by [Birch reduction](/source/Birch_reduction) of [estrone methyl ether](/source/estrone_methyl_ether) to [nandrolone](/source/nandrolone) and back-oxidation of the reduced 17-keto group.<ref>{{cite journal | vauthors=((Krohn, K.)), ((Vinke, I.)), ((Adam, H.)) | journal=The Journal of Organic Chemistry | title=Transition-Metal Catalyzed Oxidations. 7. Zirconium-Catalyzed Oxidation of Primary and Secondary Alcohols with Hydroperoxides | volume=61 | issue=4 | pages=1467–1472 | date=1 January 1996 | url=https://pubs.acs.org/doi/10.1021/jo9518720 | doi=10.1021/jo9518720| url-access=subscription }}</ref> Protecting the 17-position with ethylene glycol obviates the need for having to perform an oxidation step.<ref>{{cite journal | vauthors=((Czakó, B.)), ((Kürti, L.)), ((Mammoto, A.)), ((Ingber, D.)), ((Corey, E.)) | journal=Synfacts | title=Synthesis of Cortistatin Analogues | volume=2009 | issue=12 | pages=1316–1316 | date= December 2009 | url=http://www.thieme-connect.de/DOI/DOI?10.1055/s-0029-1218326 | doi=10.1055/s-0029-1218326| url-access=subscription }}</ref>

The semi-synthesis uses [sitolactone](/source/sitolactone) as the starting material.<ref>刘喜荣 & 曾春玲, CN104497088 (2015 to HUNAN XINHEXIN BIOLOGICAL PHARMACEUTICAL Co Ltd).</ref><ref>Joel Edward Kalamazoo Mich. Huber, DE3208432 (1983 to Pharmacia and Upjohn Co).</ref><ref>Joel E. Huber, {{US patent|4400524}} (1983 to Pharmacia and Upjohn Co).</ref>

Bolandione finds use in the synthesis of [norethandrolone](/source/norethandrolone),<ref>Left Power, et al. CN115286672 (2022 to Huanggang Renfu Pharmaceutical Co ltd) </ref> [norethindrone](/source/norethindrone), and [normethandrone](/source/normethandrone). Bolandione finds use in the synthesis of [6-dehydronandrolone acetate](/source/6-dehydronandrolone_acetate),<ref>Zeng Chunling, et al. CN118290508 (2024 to Hunan Xinhexin Biological Medicine Co ltd).</ref> a chemical with application in the synthesis of [fulvestrant](/source/fulvestrant), [tibolone](/source/tibolone), [mibolerone](/source/mibolerone), and [isotibolone](/source/isotibolone). A further use for bolandione is in the synthesis of [19-nordehydroepiandrosterone](/source/19-nordehydroepiandrosterone).<ref>Tang Sihua, et al. CN117820407 (2024 to Hubei Tongtong Steroidal Drug Research Institute Co ltd).</ref> One further use of bolandione is in the synthesis of [allylestrenol](/source/allylestrenol).<ref>郑正春, et al. CN102225960 (2012 to Beijing Keyifeng Biotech Development Co ltd).</ref> Bolandione finds use in the synthesis of [Segesterone acetate](/source/Segesterone_acetate).

== See also ==
* [List of androgens/anabolic steroids](/source/List_of_androgens%2Fanabolic_steroids)

== References ==
{{Reflist}}

{{Androgen receptor modulators}}
{{Estrogen receptor modulators}}
{{Progesterone receptor modulators}}

Category:Androgens
Category:Designer prodrugs
Category:Diketones
Category:Estranes
Category:Estrogens
Category:Progestogens

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Adapted from the Wikipedia article [Bolandione](https://en.wikipedia.org/wiki/Bolandione) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Bolandione?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.