The synthesis of potential steroid receptor antagonists
The first section of this thesis presents a review of the literature on endocrine hormones, synthetic steroids, and synthetic steroid receptor antagonists. Particular emphasis is placed upon the estrogen, progesterone and glucocorticoid activity of these compounds. The structure, activity and preparation of some progesterone/glucocorticoid receptor antagonists is also reviewed. The second section of this thesis presents a route for the synthesis of 19-aryl substituted androstanes. These compounds have been designed to explore their potential antiprogestational and antiglucocorticoid activity. It is demonstrated that a bulky aromatic functionality may be introduced at the sterically hindered C-19 methyl group, by the nucleophilic attack of an organometallic nucleophile on a 10~-formyl-19-norandrostane, which is suitably protected at positions C-3 and C-17. The subsequent careful manipulation of the C-3 and C-17 functionalities has led to a succesful 11 step synthesis (scheme 4.19) of 17~-hydroxy-17a-(prop-l-yne)-19-(p-N,N- dimethylaminophenyl)androst-5-en-3-one (3.1), which should be of interest for biological evaluation.