Progestin

The classical progestins as well as the corticosteroids arc based on a steroid nucleus that incorporates a two-carbon side chain at the 17 position that often includes a carbonyl group at position 21. The hypothetical parent hydrocarbon has been assigned the name pregnane for purposes of nomenclature. While two classes of compounds, progestins and corticoids, share common biosynthetic pathways, their biological activities differ markedly. 

Progesterone ranks with estradiol as one of the key hormones that controls the reproductive cycle in the mammalian female. Progesterone, synthesized by a structure on the ovary that forms immediately after ovulation known as the corpus luteum, inhibits subsequent ovulation until the next cycle. Increased levels of progesterone are essential in 

Strategies for Organic Drug Synthesis and Design, Second Edition. By Daniel Lednicer Copyright 2009 John Wiley Sons, Inc. 

Solvolysis of this leads to the reverse rearrangement and restoration of the homoallyl alcohol function (6-4), with the net addition of a methyl group at the 6 position. 

The product (6-4) from that sequence, which is of course simply 6-methyldios-genin, is then subjected to a series of degradation reactions as those used for the parent compound to give the 6-methyl derivative (7-1) of dehydropregnenolone. Reaction of the enone function of that product with diazomethane leads to 1,3-dipolar addition and the formation of the pyrrazoline (7-2). That intermediate loses 

In summary, an effective resolution of even the most complex mixtures of steroids may be achieved by using a combination of normal and reversed phase chromatography. 

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Table 2. Progestins Marketed in the United States and Europe for Contraceptive and Noncontraceptive Uses...

Gestodene Gestodene (54), along with norgestimate and desogestrel, are the progestin components of the third-generation oral contraceptives (see Contraceptives). It may be crystallised from hexane/acetone (81) or ethyl acetate (82), and its crystal stmcture (83) and other spectral data have been reported (84). 

X-Ray Crystallography. Structural data exists on more than one thousand steroids. Comparisons of the conformations obtained by x-ray crystallography have been made to the conformations obtained by other methods (161). Several studies use x-ray crystal stmctures in the study of progestins. 

Quantitative Structure—Activity Relationships. Many quantitative stmcture—activity relationship (QSAR) studies of progestins have appeared in the Hterature and an extensive review of this work is available (174). QSAR studies attempt to correlate electronic, steric, and/or hydrophobic properties to progestational activity or receptor binding affinity. A review focusing on the problems associated with QSAR of steroids has been pubUshed (175). 

Assay Methods for Evaluating Progestin Agonists and Antagonists. 

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