Steroids. 2. Synthesis of C-18 functionalized steroids via the Smith-Hughes route

The total synthesis of a series of racemic C-18 functionalized steroids was carried out in a search for novel estrogen-and/or progestin-receptor agonists or antagonists. The target compound 3,18-dihydroxyestra-1,3,5(10)-triene (2), 13-(2-oxopropyl)gona-4-en-3-one (3), 13-(1-hydroxy-1-prop-2-ynyl)gona-4-en-3-one (4a and 4b) and 13-(1-acetoxy-2-oxo-1-propyl)gona-4-en-3-one (5) are position isomers of the highly biologically active estradiol, progesterone, norethindrone, and 17-acetoxyprogesterone, respectively. Nevertheless the synthetic C-18 functionalized steroids 3-5 showed little activity in the Clauberg and anti-Clauberg assays. Compound 2 showed no antagonism in the postcoital assay despite the fact that it exhibited weak but measurable in vitro receptor-binding activity.