山莨菪碱和樟柳碱的衍生物——季铵盐及氮氧化合物的合成
SYNTHESIS OF QUATERNARY AMMONIUM SALTS AND N-OXIDES OF ANISODAMINE AND ANISODINE
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摘要: 为了寻找外周抗胆碱作用强的托品类药物,合成了山莨菪碱和樟柳碱的类似物(Ⅲ和Ⅳ)、溴甲烷季铵盐(Ⅴ~Ⅷ)和硫酸甲酯季铵盐(Ⅸ和Ⅹ)。在探索向肌性较强的脏器解痉药方面,合成了这两个碱的溴正丁烷季铵盐(Ⅺ和Ⅻ)及氮氧化合物(ⅩⅣ和ⅩⅤ)。化合物(Ⅲ~ⅩⅤ)的物理常数及核磁共振光谱数据分别列于表1和表2。这些化合物的抗胆碱活性筛选结果表明,甲基季铵盐比其母体碱的活性强,其中以山莨菪碱溴甲烷季铵盐的活性最强。Abstract: In order to search for effective peripheral anticholinic atropine type drugs, Nmethylbromides(Ⅴ-Ⅵ), N-methylmethosulfates (Ⅸ and Ⅹ) and N-oxides (ⅩⅣ and ⅩⅤ) of anisodamine and anisodine were prepared. In exploring stronger musculotropic organic antispasmodics, n-butyl bromide derivatives of both alkaloids were also prepared (Ⅺ and Ⅻ). Deoxyanisodine (Ⅲ) was obtained as a minor product on hydrogenation of anisodine. Physical and NMR spectral data of these derivatives and related compounds were listed in tables 1 and 2 respectively. The anticholinic screening results showed that N-methyl bromide quaternary ammonium salts were more active than their parent compounds. Among them anisodamine-N-methyl bromide (Ⅴ) is the most active.
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