SYNTHESIS OF AN ORAL CONTRACEPTIVE QUINGESTANOL

Quingestanol (Ⅰ) is a potent progestational agent with prolonged activity, and is used as an oral contraceptive. It was formerly obtained in 4 steps from 19-norandrost-4-en-3, 17-dione (Ⅴ). We wish to report now the synthesis in two steps from dione (Ⅴ) by etherification with cyclopentanol, triethyl orthoformate and a catalytic amount of p-toluenesulfonic acid followed by ethynylation with sodium acetylide and concomitant acetylation. When dione (Ⅴ) was treated with the same ethynylation-acetylation procedure, 17α-ethynyl-19-nortestosterone-3, 17-diacetate (Ⅶ) was obtained, thus the supposition₍₉₎ made previously was verified that the Δ₄-3-one in (Ⅴ)was enolized to Δ_3,5-diene-3-ol ion (Ⅷ) during ethynylation. The enol acetate (Ⅶ)could be converted into quingestanol (Ⅰ) according to the method reported.