Almestrone

Almestrone
Clinical data
Other namesBa 38372; Ciba 38372; 7α-Methylestrone
Routes of
administration		By mouth
Drug classEstrogen
ATC code
  • None
Identifiers
  • (7R,8R,9S,13S,14S)-3-hydroxy-7,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.212.018
Chemical and physical data
FormulaC19H24O2
Molar mass284.399 g·mol−1
3D model (JSmol)
  • CC1CC2=C(C=CC(=C2)O)C3C1C4CCC(=O)C4(CC3)C
  • InChI=1S/C19H24O2/c1-11-9-12-10-13(20)3-4-14(12)15-7-8-19(2)16(18(11)15)5-6-17(19)21/h3-4,10-11,15-16,18,20H,5-9H2,1-2H3/t11-,15-,16+,18-,19+/m1/s1
  • Key:JUAJXSMWFOFDFC-MNHDCVOLSA-N

Almestrone (INNTooltip International Nonproprietary Name) (developmental code names Ba 38372, Ciba 38372), also known as 7α-methylestrone, is a synthetic, steroidal estrogen which was synthesized in 1967 but was never marketed.[1] It is used as a precursor in the synthesis of several highly active steroids.[2][3]

Applications

Almestrone had application in the original synthesis of Tibolone by Organon.[4][5][6] However this method of synthesis is now thought to be largely obsolete. Tibolone is used to synthesize ERA-63.

The synthesis of Dimethandrolone,[7] or the closely related PC10125553.[8]

Almestrone has practical application in the synthesis of Dimethyldienolone & Dimethyltrienolone. They share the same precursor compound which is called 7alpha-Methyl-estra-4,9(10)-diene-3,17-dione.

Another use for almestrone is in the synthesis of TAS-108.[9]

Almesterone methyl ether can be used to make 19-nor-D-homosteroids (c.f. mibolerone).[10]

Synthesis

The original synthesis of almestrone is quite old and dates back to 1967:[11][12] Aromatization method:[13] Precursor:[14]

The dehydrogenation of testosterone propionate [57-85-2] (1) by chloranil gives the corresponding 4,6-diene, [25862-97-9] (2). Conjugate addition of methylmagnesium bromide gives, after saponification, 7-alpha-Methyltestosterone (U 14103) [7642-58-2] (3) along with some of the 7β-epimer. Oxidation of the alcohol with pyridinium chlorochromate gives 7alpha-Methylandrost-4ene-3,17-dione, PC23383196 (4). Oxidation with DDQ gives 7alpha-methyl-1,4-androstadiene-3,17-dione, PC54064745 (5). It is likely that the direction of this second dehydrogenation is mandated by the presence of the methyl group at C-7; this group may hinder the approach of reagent to the center which would lead to the alternate diene. Ketalization with ethylene glycol afforded PC26864627 (6). Elimination of the angular methyl group at C-19 with consequent aromatization is achieved by treatment of the diene with lithium in the presence of biphenyl. Dektalization afforded Almestrone [10448-96-1] (7).

It can also be made from dehydronandrolone acetate.[15] 7a-Methyl-estra-4-en-3,17-dione (Mentabolan) [17000-78-1] is oxidized with a catalytic amount of a copper halide in the presence of oxygen.[16]

The chemical synthesis starting from trestolone acetate has been described (but this is old work).[17]

See also

References

  1. ^ Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 900–. ISBN 978-1-4757-2085-3.
  2. ^ Krause N, Aksin-Artok Ö (2011). "Copper-Mediated and Copper-Catalyzed Addition and Substitution Reactions of Extended Multiple Bond Systems". PATai's Chemistry of Functional Groups. doi:10.1002/9780470682531.pat0450. ISBN 978-0-470-68253-1.
  3. ^ Morais GR, Yoshioka N, Watanabe M, Mataka S, Oliveira CD, Thiemann T (2006). "C7-Substituted Estranes and Related Steroids". Mini-Reviews in Organic Chemistry. 3 (3): 229–251. doi:10.2174/1570193X10603030229. ISSN 1570-193X.
  4. ^ Wieland, P., Anner, G. (January 1967). "Synthese von 7α‐Methyl‐3‐oxo‐Δ 4,9,11 ‐19‐norandrostatrienen. Über Steroide, 211. Mitteilung". Helvetica Chimica Acta. 50 (6): 1453–1461. doi:10.1002/hlca.19670500602.
  5. ^ Lednicer, D. (2011). Steroid chemistry at a glance. Wiley. ISBN 978-0-470-66084-3.
  6. ^ NL 6406797 idem Jongh Hendrik Paul De, Nicolaas Pieter Van Vliet, US3340279 (1967 to Organon).
  7. ^ Richard Blye & Hyun Kim, US20030069215 (to US Department of Health and Human Services, Government of the United States of America)
  8. ^ Richard P. Blye, et al. WO2003045398 (to US Department of Health and Human Services).
  9. ^ Masato Tanabe, et al. WO1999033859 (to SRI International Inc).
  10. ^ Jaap Van Der Louw, et al. WO2005061528 (to Akzo Nobel NV).
  11. ^ Wieland, P., Anner, G. (January 1967). "Synthese von 7α‐Methylöstron. Über Steroide, 210. Mitteilung". Helvetica Chimica Acta. 50 (1): 289–296. doi:10.1002/hlca.19670500136.
  12. ^ Kalvoda, J., Krähenbühl, Ch., Desaulles, P. A., Anner, G. (January 1967). "7α‐Methylöstrogene. Über Steroide, 209. Mitteilung". Helvetica Chimica Acta. 50 (1): 281–288. doi:10.1002/hlca.19670500135.
  13. ^ Dryden, H. L., Webber, G. M., Wieczorek, J. J. (February 1964). "The Reductive Aromatization of Steroidal Dienones. A New Method for the Preparation of Estrone". Journal of the American Chemical Society. 86 (4): 742–743. doi:10.1021/ja01058a048.
  14. ^ Ruzicka, L., Bosshard, W. (January 1937). "Sexualhormone XXI. Über zweifach ungesättigte Ketone der Androstanreihe". Helvetica Chimica Acta. 20 (1): 328–332. doi:10.1002/hlca.19370200148.
  15. ^ Zeng Chunling, et al. CN118290508 (2024 to Hunan Xinhexin Biological Medicine Co ltd).
  16. ^ Kuniaki Tatsuta, Kazuo Maruhashi, & Shingo Yano, WO2007049672 (to Taiho Pharmaceutical Co Ltd).
  17. ^ , FR1434172 (1966 to Novartis AG, BASF Schweiz AG).


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