谢晶曦, 周瑾, 贾效先, 刘春雪, 徐慧琴, 房安石, 王今之, 夏伯阳. 山莨菪碱的全合成J. 药学学报, 1980, 15(7): 403-409.
引用本文: 谢晶曦, 周瑾, 贾效先, 刘春雪, 徐慧琴, 房安石, 王今之, 夏伯阳. 山莨菪碱的全合成J. 药学学报, 1980, 15(7): 403-409.
Xie Jingxi, Zhou Jin, Jia Xiaoxian , Liu Chunxue XU Huiqin, Fang Anshi, Wang Jinzhi , Xia Boyang, . STUDIES ON THE SYNTHESIS OF ANISODAMINEJ. Acta Pharmaceutica Sinica, 1980, 15(7): 403-409.
Citation: Xie Jingxi, Zhou Jin, Jia Xiaoxian , Liu Chunxue XU Huiqin, Fang Anshi, Wang Jinzhi , Xia Boyang, . STUDIES ON THE SYNTHESIS OF ANISODAMINEJ. Acta Pharmaceutica Sinica, 1980, 15(7): 403-409.

山莨菪碱的全合成

STUDIES ON THE SYNTHESIS OF ANISODAMINE

  • 摘要: 山莨菪碱为一新胆碱能神经阻滞药。毒性低,外周作用比中枢作用强。全合成是以呋喃为原料,合成6β-羟基托品酮,将羟基乙酰化后,再将3-位酮基催化还原为α-羟基,然后用乙酰托品酰氯酯化、水解而得。本文主要报道6β-乙酰氧基托品醇与乙酰托品酰氯的酯化反应及酯化物水解合成山莨菪碱的研究。该方法现已由工厂正式投产,药品名654-2。

     

    Abstract: The alkaloid anisodamine (Ⅴ) was isolated from the medicinal plant Anisodus tanguticus (Maxim)Pascher. On the basis of pharmacological and clinical studies, anisodamine is used as a new anticholinergic drug for the treatment of acute microcirculatory disturbance.The present paper describes the total synthesis of anisodamine. It was prepared by the following steps. (1) 6β-Hydroxytropinone was formed according to the well-known Robinson's method by using furan as the starting material. (2) Treatment of 6-hydroxytropinone with pyridine and acetic anhydride gave 6β-acetoxy-tropinone, which was. converted to 6β-acetoxy-3α-hydroxytropane by catalytic hydrogenation. (3)Esterification. of 6β-acetoxy-3α-hydroxytropane with O-acetyltropoyl chloride proceeded smoothly by refluxing in chloroform. (4) Partial hydrolysis of the 6-acetoxy group was accomplished by heating the ester in 5% HCl for 1/2 to 1 hour, the exact duration being monitored by thin-layer chromatography in order to avoid the concomitant cleavage of the more hindered 3α-ester linkage.The ultraviolet, NMR and mass spectra of synthetic anisodamine were identical with those of the natural alkaloid. IR spectra of synthetic and natural specimens in the solid phase were different, since the former is a diastereomeric mixture. However, sample containing one mole of benzene of crystallization showed unexpectively identical IR spectra. Pharmacologically the synthetic product possesses comparable effects as natural anisodamine. Now it is being produced commercially with the trade name '654-2'.

     

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