Chemistry:Almestrone

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Almestrone (INN) (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]

Almestrone had application in the original synthesis of Tibolone by Organon.[4][5] However this method of synthesis is now obsolete.

Synthesis

The original synthesis of almestrone is quite old and dates back to 1967:[6][7] Aromatization method:[8] Precursor:[9]

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.[10] 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.[11]

See also

References

  1. ↑ The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 900–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA900. 
  2. ↑ "Copper-Mediated and Copper-Catalyzed Addition and Substitution Reactions of Extended Multiple Bond Systems". PATai's Chemistry of Functional Groups. 2011. doi:10.1002/9780470682531.pat0450. ISBN 978-0-470-68253-1. 
  3. ↑ "C7-Substituted Estranes and Related Steroids". Mini-Reviews in Organic Chemistry 3 (3): 229–251. 2006. doi:10.2174/1570193X10603030229. ISSN 1570-193X. 
  4. ↑ Lednicer, D. (2011). Steroid chemistry at a glance. Wiley. ISBN 978-0-470-66084-3. 
  5. ↑ NL 6406797 idem Jongh Hendrik Paul De, Nicolaas Pieter Van Vliet, US3340279 (1967 to Organon).
  6. ↑ "Synthese von 7α‐Methylöstron. Über Steroide, 210. Mitteilung". Helvetica Chimica Acta 50 (1): 289–296. January 1967. doi:10.1002/hlca.19670500136. https://onlinelibrary.wiley.com/doi/10.1002/hlca.19670500136. 
  7. ↑ "7α‐Methylöstrogene. Über Steroide, 209. Mitteilung". Helvetica Chimica Acta 50 (1): 281–288. January 1967. doi:10.1002/hlca.19670500135. https://onlinelibrary.wiley.com/doi/10.1002/hlca.19670500135. 
  8. ↑ "The Reductive Aromatization of Steroidal Dienones. A New Method for the Preparation of Estrone". Journal of the American Chemical Society 86 (4): 742–743. February 1964. doi:10.1021/ja01058a048. https://pubs.acs.org/doi/abs/10.1021/ja01058a048. 
  9. ↑ "Sexualhormone XXI. Über zweifach ungesättigte Ketone der Androstanreihe". Helvetica Chimica Acta 20 (1): 328–332. January 1937. doi:10.1002/hlca.19370200148. https://onlinelibrary.wiley.com/doi/10.1002/hlca.19370200148. 
  10. ↑ Zeng Chunling, et al. CN118290508 (2024 to Hunan Xinhexin Biological Medicine Co ltd).
  11. ↑ Kuniaki Tatsuta, Kazuo Maruhashi, & Shingo Yano, WO2007049672 (to Taiho Pharmaceutical Co Ltd).




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