王晓鸣, 恽榴红, 文广伶, 张其楷. 抗胆碱能化合物3-甲基-3-氮杂双环3,3,1壬-9-酯类α,β异构体的合成J. 药学学报, 1984, 19(10): 748-754.
引用本文: 王晓鸣, 恽榴红, 文广伶, 张其楷. 抗胆碱能化合物3-甲基-3-氮杂双环3,3,1壬-9-酯类α,β异构体的合成J. 药学学报, 1984, 19(10): 748-754.
WANG Xiao-Ming, YUN Liu-Hong, WEN Guang-Ling , ZHANG Qi-Kai, . ANTICHOLINERGICS:SYNTHESIS OF α,β ISOMERS OF 3-METHYL-3-AZABICYCLO3, 3, 1 NONAN-9-YL ESTERSJ. Acta Pharmaceutica Sinica, 1984, 19(10): 748-754.
Citation: WANG Xiao-Ming, YUN Liu-Hong, WEN Guang-Ling , ZHANG Qi-Kai, . ANTICHOLINERGICS:SYNTHESIS OF α,β ISOMERS OF 3-METHYL-3-AZABICYCLO3, 3, 1 NONAN-9-YL ESTERSJ. Acta Pharmaceutica Sinica, 1984, 19(10): 748-754.

抗胆碱能化合物3-甲基-3-氮杂双环3,3,1壬-9-酯类α,β异构体的合成

ANTICHOLINERGICS:SYNTHESIS OF α,β ISOMERS OF 3-METHYL-3-AZABICYCLO3, 3, 1 NONAN-9-YL ESTERS

  • 摘要: 本文报道了一系列抗胆碱能化合物3-甲基-3-氮杂双环3,3,1壬-9-酯类αβ异构体的合成。将3-甲基-3-氮杂双环3,3,1壬-9-酮还原为相应的醇后,分离成9α和9β两种异构醇,再分别与各种取代羧酸甲酯进行酯交换,而得αβ酯类。对所有产物的立体构型与1H核磁共振谱的关系进行了讨论。初步药理实验结果表明,除化合物Ⅲ9,Ⅲ10外,所有化合物均具有较强的中枢抗胆碱能作用,其中6个化合物的抗摈榔碱震颤作用强度接近或超过阿托品,相应的αβ异构体之间作用强度差别较小。

     

    Abstract: A series of α-and β-isomers of 3-methyl-3-azabicyclo-3,3,1 nonan-9-yl substituted carboxylic esters were synthesized. The starting material 3methyl-3-azabicyclo 3,3,1 nonan-9-one was prepared from cyclohexanone, methylamine and formaldehyde by Mannich reaction. The ketone was reduced and separated into 9α and 9β alcohols, and the isomeric alcohols were esterified separately with various methyl carboxylates to give the corresponding esters Ⅲ1~10. The stereochemistry of these esters were identified by means of 1HNMR.Preliminary pharmacological results showed that, except compounds Ⅲ9 and Ⅲ10 all compounds exhibited potent central anticholinergic activities, six of them were equal to or more potent than atropine. The α and β isomers of each pair were close in their anticholinergic activity in 9α, βisomers of 3-methyl-3-azabicyclo 3,3,1 nonanyl esters.

     

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