Doisynoestrol

Last updated
Doisynoestrol
Doisynoestrol.svg
Clinical data
Trade names Fenocyclin, Surestrine, Surestryl
Other namesDiosynestrol; Fenocycline; Fenocyclin; Phenocyclin; RS-2874; Dehydrofolliculinic acid; cis-Bisdehydrodoisynolic acid 7-methyl ether; BDDA ME; NSC-56846; NSC-122041
Routes of
administration 		By mouth
Drug class Nonsteroidal estrogen
Identifiers
  • 1-Ethyl-7-methoxy-2-methyl-3,4-dihydro-1H-phenanthrene-2-carboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C19H22O3
Molar mass 298.382 g·mol−1
3D model (JSmol)
  • CCC1C2=C(CCC1(C)C(=O)O)C3=C(C=C2)C=C(C=C3)OC
  • InChI=1S/C19H22O3/c1-4-17-16-7-5-12-11-13(22-3)6-8-14(12)15(16)9-10-19(17,2)18(20)21/h5-8,11,17H,4,9-10H2,1-3H3,(H,20,21)
  • Key:HZZSXUIUESWVSS-UHFFFAOYSA-N

Doisynoestrol (brand names Fenocyclin, Surestrine, Surestryl; former developmental code name RS-2874), also known as fenocycline, as well as cis-bisdehydrodoisynolic acid 7-methyl ether (BDDA ME), is a synthetic nonsteroidal estrogen of the doisynolic acid group that is no longer marketed. [1] [2] It is a methyl ether of bisdehydrodoisynolic acid. [1] Doisynoestrol was described in the literature in 1945. [1] It has about 0.02% of the relative binding affinity of estradiol for the estrogen receptor. [3]

Contents

Acitivity

The methyl ether has the same activity as the alcohol making it one of the most potent oral estrogens ever discovered. [4]

Synthesis

The chemical synthesis has been described by Johnson & Graber: [5] [6] [7] German method: [8] [9] [10] Unavailable method: [11]

Doisynoestrol synthesis.svg

The Stobbe condensation between 2-propionyl-6-methoxynaphthalene (Promen) [2700-47-2] (1) and diethyl succinate [123-25-1] (2) gives a mixture of unsaturated esters (3). Catalytic hydrogenation of the olefin and saponification of the ester yields (4). Intramolecular cyclization occurs first by reaction with acetyl chloride then with aluminium trichloride in nitromethane solvent to give 1-Ethyl-7-methoxy-4-oxo-1,3,4-tetrahydro-phenanthrene-2-carboxylic acid, PC287656 (5). Catalytic hydrogenation in the presence of perchloric acid led to reductive removal of the keto group in the newly formed ring giving 1-Ethyl-7-methoxy-1,2,3,4-tetrahydrophenanthrene-2-carboxylic acid, PC177705457 (6). Esterification of the remaining acid moiety in the presence of diazomethane gave Methyl 1-ethyl-7-methoxy-1,2,3,4-tetrahydrophenanthrene-2-carboxylate, PC151271 (7). Alkylation by means of triphenylmethyl sodium in the presence of iodomethane gave methyl 1-ethyl-7-methoxy-2-methyl-3,4-dihydro-1H-phenanthrene-2-carboxylate, PC162092603 (8). Lastly saponification of the ester completed the synthesis of Bisdehydrodoisynolic acid.

See also

References

  1. 1 2 3 Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 465–. ISBN   978-1-4757-2085-3.
  2. ↑ Herbai G (October 1971). "Separation of growth inhibiting potency from oestrogenicity in different weak oestrogenic drugs of various chemical structures". Acta Endocrinologica. 68 (2): 249–63. doi:10.1530/acta.0.0680249. PMID   5171465.
  3. ↑ Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM (March 2000). "The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands". Toxicol Sci. 54 (1): 138–53. doi: 10.1093/toxsci/54.1.138 . PMID   10746941.
  4. ↑ Miescher, K. (1 December 1948). "On Doisynolic Acids, A New Class of Estrogens". Chemical Reviews. 43 (3): 367–384. doi:10.1021/cr60136a001.
  5. ↑ Johnson, W. S., Graber, R. P. (July 1948). "BIS-DEHYDRODOISYNOLIC ACID". Journal of the American Chemical Society. 70 (7): 2612–2613. doi:10.1021/ja01187a525.
  6. ↑ William S Johnson & Robert P Graber, U.S. patent 2,574,396 (1951 to Individual).
  7. ↑ William S Johnson & Robert P Graber, U.S. patent 2,683,738 (1954 to Individual).
  8. ↑ Heer, J., Billeter, J. R., Miescher, K. (January 1945). "Über Steroide. 43. Mitteilung. Totalsynthese der racemischen Bisdehydro‐doisynolsäuren. Über oestrogene Carbonsäuren IV". Helvetica Chimica Acta. 28 (1): 1342–1354. doi:10.1002/hlca.6602801186.
  9. ↑ Miescher Karl & Anner Georg, U.S. patent 2,459,949 (1949 to CIBA PHARMACEUTICAL PRODUCTS Inc).
  10. ↑ Miescher Karl, Heer Jules, & Anner Georg, U.S. patent 2,621,208 (1952 to CIBA PHARMACEUTICAL PRODUCTS Inc).
  11. ↑ Gastambide-Odier, M. et al, Bull. Soc. Chim. Fr., 1963, 1777.



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