Synthesis and biological inactivity of some 4alpha,6-cyclo steroids

Two different synthetic routes have been used to synthesize a series of cyclopropyl conjugated ketones in which 4alpha,6-unsaturation replaces the usual 4,5-unsaturation. The synthetic routes involve intramolecular ketocarbene addition to a 5-6 double bond and intramolecular 1,3-elimination of 6beta-substituted 5beta-3-keto steroids. Both routes give 5beta products. The analogs of progesterone, testoterone acetate, and norethisterone have been prepared and shown to be remarkably biologically inactive when compared with the corresponding standard. Possible reasons for such inactivity are discussed.