郑长胜, 谢晶曦. 山莨菪碱四个光学异构体的合成和分离J. 药学学报, 1991, 26(2): 96-102.
引用本文: 郑长胜, 谢晶曦. 山莨菪碱四个光学异构体的合成和分离J. 药学学报, 1991, 26(2): 96-102.
CS Zheng, JX Xie. SEPARATION AND RESOLUTION OF FOUR STEREOISOMERS OF ANISODAMINEJ. Acta Pharmaceutica Sinica, 1991, 26(2): 96-102.
Citation: CS Zheng, JX Xie. SEPARATION AND RESOLUTION OF FOUR STEREOISOMERS OF ANISODAMINEJ. Acta Pharmaceutica Sinica, 1991, 26(2): 96-102.

山莨菪碱四个光学异构体的合成和分离

SEPARATION AND RESOLUTION OF FOUR STEREOISOMERS OF ANISODAMINE

  • 摘要: 以6-(甲氧)亚甲氧基托品酮(Ⅰ)为原料,与(+)L-酒石酸或(-)D-酒石酸成盐,可分离得到右旋的6-(甲氧)亚甲氧基托品酮(+)Ⅰ和左旋的6-(甲氧)亚甲氧基托品酮(-)Ⅰ.(+)Ⅰ和(-)Ⅰ氢化还原后,分别与α-甲酰基苯乙酸甲酯进行酯交换,硼氢化钠还原侧链上醛基,水解脱去羟基保护基得到左旋山良菪碱(-)Ⅳ和右旋山莨菪碱(+)Ⅳ.(-)Ⅳ和(+)Ⅳ分別与(-)二苯甲酰酒石酸和(+)二苯甲酰酒石酸成盐,可用分步结晶法拆分到山崀菪碱的四个光学异构体。

     

    Abstract: Four stereo-isomers of anisodamine were obtained by two consecutive resolutions. (+) 6-Methoxy methoxy tropinone (+Ⅰ) and its optical antipode (-Ⅰ) could be obtained by the resolution of racemic (Ⅰ) with (+) L-tartaric acid and (-) D-tartaric acid respectively. Subsequent catalytic hydrogenation of the optically active compound Ⅰ, then ester exchange with methyl 2-formyl-2-phenyl acetate followed by reduction with NaBH4 and cleavage of hydroxyl protective group in acid condition, the corresponding optically active (+) Ⅳ and (-) Ⅳ were obtained. Compound (+) Ⅳ was treated with (+) dibenzoyltartaric acid and (-) Ⅳ by (-)dibenzoyltartaric acid, The epimeric salts were separated and purified by fractional crystallization from absolute alcohol. Four stereoisomers of anisodamine (6S, 2′S; 6S, 2′R; 6R, 2′R and 6R, 2′S) were thus obtained by neutralization of the corresponding salts.

     

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