Synthesis of 11 beta,13 beta- and 13 beta,16 beta-propano steroids: probes of hormonal activity.
Syntheses of 11 beta,13 beta- and 13 beta,16 beta-propano derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one are described. The 13 beta,16 beta bridge was constructed by intramolecular alkylation of the C-16 enolate anion from 3-methoxy-13 beta-[3'-(tosyloxy)propyl]gona-3,5-dien-17-one, the latter being obtained via Birch reduction of both aryl groups of 17 beta-hydroxy-3-methoxy-13 beta-(3'-phenoxypropyl)gona-1,3,5(10),8-tetraene (1). The 11 beta,13 beta bridge was constructed by Prins cyclization of 17 beta-acetoxy-3-methoxy-13 beta-(3'-oxopropyl)gona-1,3,5(10),9(11)-tetraene, itself obtained via Birch reduction of only the side-chain aryl group of 1. Binding affinities of certain of these compounds and substituted 13 beta-propyl derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one for the uterine cytosol receptor of progesterone are reported, and the origin of the high progestational activity of norgestrel and 11 beta-substituted progestins is discussed.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D066298:In Vitro Techniques; D011374:Progesterone / Q000037:antagonists & inhibitors; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D013256:Steroids / Q000138:chemical synthesis* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
D011956:Receptors, Cell Surface; D013256:Steroids; D011374:Progesterone