More Progesterone Analogues

Many of the foregoing modified progesterone analogues exhibit improved biopharmaceutical properties over progesterone proper. The derivatives that follow were likely prepared in the hope that combinations of substituents would lead to additive improvements, a circumstance that often prevails in the pregnane series. 

Mineral acid causes that product to dehydrate, in the process restoring the 4,6-diene 23-10. Reaction with acetic anhydride under forcing conditions leads to acylation of the 17-hydroxyl group. That acetate, clomegestone (23-11), is somewhat more potent than its 17-desoxy congener clometherone (22-7). 

Reaction of this last intermediate with methylmagnesium bromide opens the epoxide that has been carried through the preceding reactions (24-5). 

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With these very positive conclusions it is not clear why micronized progesterone has not been more widely used. Commercial factors may well have played a role in maintaining the overwhelming dominance of the patented synthetic progestogens. On the other hand, despite the fact that there are estimated to be 500 000 current users of micronized progesterone in France alone, the worldwide scope of experience is stiU limited compared with that of the sjmthetic analogues, and one must be prepared for surprises if this product should ever be used more widely. It... 

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