抗胆碱能药物的研究 3-取代托品衍生物的合成

本文报道24个3-取代托品乙醇类、乙烯类和乙烷类化合物的合成。药理筛选结果表明:大多数化合物有明显的抗胆碱能作用,且中枢与外周作用相当。

STUDIES ON ANTICHOLINERGICS:SYNTHESIS OF 3-SUBSTITUTED TROPANE DERIVATIVES

Twenty-four 3-substituted tropanyl ethanols, ethenes and ethanes were synthesized with 3-tropanone as starting material. Through Wittig reaction, hydrogenation and Grignard reaction, 3-substituted tropanylmethyl ketones (Ⅳ_1～6) were obtained.By catalytic hydrogenation of ketone Ⅳ₁, the corresponding alcohol Ⅴ₁ was easily obtained. The ketones Ⅳ_2～6 were reacted with corresponding bromides and lithium to form the corresponding alcohols Ⅴ_2～6. However, the alcohols (V_7～8)could be obtained directly from ethyl (3-tropanyl) acetate, the corresponding bromide and lithium. By dehydration of the alcohols V, the corresponding alkenes VI were formed. The alkenes VI gave the corresponding alkanes VII through catalytic hydrogenation.The anticholinergic action of all these compounds were tested preliminarily in mice and most of them exhibited marked actions. The structure-activity relationship was briefly discussed.