C-Nor-9,11-secoestranes as modified estrogens and fertility regulation

• Published in: Journal of medicinal chemistry 1988-06, Vol.31 (6), p.1261-1264
• Main Authors: Lal, Kasturi, Sharma, Indra, Agarwal, A. K, Agnihotri, Anila, Ray, Suprabhat
• Format: Article
• Language: English
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Animals; Chemistry; Estranes - chemical synthesis; Estranes - pharmacology; Estrogens - chemical synthesis; Estrogens - pharmacology; Exact sciences and technology; Female; Fertility - drug effects; Molecular Conformation; Organic chemistry; Preparations and properties; Rats; Secosteroids - chemical synthesis; Secosteroids - pharmacology; Steroids; Structure-Activity Relationship; Uterus - drug effects
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00401a033

The synthesis of C-nor-9,11-secoestradiol (4) has been achieved from 17 beta-acetoxy-11-chloro-3-methoxy-C-nor-9,11-secoestra-1,3,5(10)-tr ien-9-one (1) through a sequence of reactions without affecting the stereochemistry of estradiol-17 beta. Removal of the 9-keto function of 1 by hydrogenolysis and its subsequent treatment with Na/NH3 gives C-nor-9,11-secoestradiol 3-(methyl ether) (3), which has been demethylated under alkaline conditions to furnish C-nor-9,11-secoestradiol (4). Pyridinium chlorochromate oxidation of 3 gives the corresponding 17-ketone 6. Jones' oxidation of 4 to the ketone 5 and reaction of 5 and 6 with lithium acetylide gives corresponding 17 alpha-ethynyl derivatives 7 and 8. Relative binding affinity to estradiol-17 beta receptors and uterotropic, antiuterotrophic, and antiimplantation activities of compounds 3-8 have been studied. The effect of conformational flexibility on ligand-receptor interaction of these compounds is discussed.