韩广甸, 杨光中, 郑多楷, 鲁桂琛, 徐惠琴, 张枝梅, 牛淑兰. 计划生育药物的合成——Ⅰ.甾体口服避孕药高诺酮的全合成J. 药学学报, 1980, 15(3): 169-174.
引用本文: 韩广甸, 杨光中, 郑多楷, 鲁桂琛, 徐惠琴, 张枝梅, 牛淑兰. 计划生育药物的合成——Ⅰ.甾体口服避孕药高诺酮的全合成J. 药学学报, 1980, 15(3): 169-174.
Han Guangdian, Yang Guangzhong, Zheng Duokai , Lu Guishen Xu Huiqin, Zhang Zhimei , Niu Shulan, . STUDIES OF SYNTHETIC CONTRACEPTIVES Ⅰ. THE TOTAL SYNTHESIS OF NORGESTRELJ. Acta Pharmaceutica Sinica, 1980, 15(3): 169-174.
Citation: Han Guangdian, Yang Guangzhong, Zheng Duokai , Lu Guishen Xu Huiqin, Zhang Zhimei , Niu Shulan, . STUDIES OF SYNTHETIC CONTRACEPTIVES Ⅰ. THE TOTAL SYNTHESIS OF NORGESTRELJ. Acta Pharmaceutica Sinica, 1980, 15(3): 169-174.

计划生育药物的合成——Ⅰ.甾体口服避孕药高诺酮的全合成

STUDIES OF SYNTHETIC CONTRACEPTIVES Ⅰ. THE TOTAL SYNTHESIS OF NORGESTREL

  • 摘要: 本文报告高诺酮(Norgestrel)(Ⅰ)的简便合成方法。即用异硫脲盐(Ⅴ)与2-乙基环戊二酮-1,3(Ⅵ)缩合得Ⅶ,然后在乙二醇中以酸为催化剂,同时进行环合和17-酮基保护,生成缩酮(Ⅷ),再经选择性氢化、锂-氨还原和水解,得双酮(Ⅺ)。双酮(Ⅺ)用乙炔-氢氧化钾选择性炔化后,即可得到60%左右的高诺酮(Ⅰ)。

     

    Abstract: 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.

     

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