Mestranol

Mestranol is the 3-methyl ether of ethinylestradiol. It was the estrogen used in many of the first oral contraceptives.

It is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver with a conversion efficiency of 70% (50 µg of mestranol is  pharmacokinetically bioequivalent to 35 µg of ethinylestradiol).

Synthesis
The reaction of 17-keto steroids with nucleophiles illustrates the high degree of stereospecifity that is maintained in many steroid reactions; approach of that carbonyl group from the b face is virtually forbidden by the presence of the adjacent 18 methyl. The reaction products consequently consist of almost pure isomers from attack at the a face.



Reaction of estrone 3-methyl ether with lithium acetylide thus leads to mestranol.