Pentacyclic Steroids. Synthesis of 4,6β-Ethanoestradiol, 4,6β-Ethanoestrone, and 17α-Ethynyl-4,6β-ethanoestradiol

Synthesis of a new series of pentacyclic steroids, 4,6β-ethanoestradiol (1), 4,6β-ethanoestrone (2), and 17α-ethynyl-4,6β-ethanoestradiol (3), is described. Estrone is converted into the key intermediate 17β-acetoxy-3-methoxy 1,3,5(10)-estratriene-6β-acetic acid (13) in 11 steps. Friedel-Crafts cyclization of the acid chloride of 13 with aluminum chloride provides compounds 14 and 15. Further structural modifications lead to 1, 2, and 3. The absolute configuration of the p-bromobenzoate derivative of 1 has been confirmed by x-ray crystallography. Fusion of the ethano bridge at positions C-4 and C-6 from the β face leads to a unique class of steroids in which the B ring assumes a highly distorted conformation.