STUDIES ON THE SYNTHESIS OF ANISODAMINE
Xie Jingxi, Zhou Jin, Jia Xiaoxian and Liu Chunxue. (Institute of Materia Medica, Chinese Academy of Medical Sciences Beijing) XU Huiqin, Fang Anshi, Wang Jinzhi and Xia Boyang (Beijing Pharmaceutical Factory)
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'.