STUDIES OF SYNTHETIC CONTRACEPTIVES Ⅰ. THE TOTAL SYNTHESIS OF NORGESTREL

Norgestrel is a steroid with potent progesterone acitivity. It has been succeeded in using 12 mg norgestrel with 3 mg quinestrol(EECPE)once a month as a new long acting oral contraceptive. The synthetic method of norgestrel is described in this report. 6-Methoxy-1, 2, 3,4-tetrahydronaphthylidene ethyl isothiuronium acetate (Ⅴ) was condensed with 2-ethyl-1, 3-cyclopentadione to give compound (Ⅶ), which was converted to (Ⅷ) in ethylene glycol using acid as a "catalyst" through cyclization and simultaneous protection of the 17-keto group. Gompound(Ⅷ)was hydrogenated, reducod and hydrolysed to give dione (Ⅺ). After selective ethynylation of dione (Ⅺ) with potassium hydroxide and acetylene in THF, the final product norgestrel (Ⅰ) was obtained in good yield.