Grunewald G L, Grindel J M, Patil P N, Salman K N
J Med Chem. 1976 Jan;19(1):10-6. doi: 10.1021/jm00223a003.
The synthesis of beta-phenylethanolamine analogs in which the phenyl ring is replaced by cyclohexyl, cyclohexen-4-yl, cyclooctyl, cyclooctenyl, cycloocta-1,3-dien-2-yl, cycloocta-1,5-dienyl, and cyclooctatetraenyl was accompanied by conversion of the corresponding aldehydes to the cyanohydrins followed by reduction with lithium aluminum hydride. A preparatively useful synthesis of 1-formylcyclooctatetraene is described utilizing the photocycloaddition of methyl propiolate to benzene followed by reduction to the alcohol and oxidation with MnO2. All compounds, as their hydrochloride salts, exhibited indirect adrenergic activity on the rat vas deferens. On the reserpinized rat vas deferens all compounds potentiated the effects of exogenous norepinephrine. The results are in agreement with the conclusion that the more saturated the ring moiety, the greater the affinity for the amine uptake site of the vas deferens and suggest that there is no important interaction between the drug and this uptake site that involves pi-complex formation.
在β-苯乙醇胺类似物的合成中，苯环被环己基、环己烯-4-基、环辛基、环辛烯基、环辛-1,3-二烯-2-基、环辛-1,5-二烯基和环辛四烯基取代，同时相应的醛转化为氰醇，随后用氢化铝锂还原。描述了一种制备上有用的1-甲酰基环辛四烯的合成方法，该方法利用丙酸甲酯与苯的光环化加成反应，随后还原为醇并用MnO₂氧化。所有化合物作为它们的盐酸盐，在大鼠输精管上表现出间接肾上腺素能活性。在利血平化的大鼠输精管上，所有化合物都增强了外源性去甲肾上腺素的作用。结果与以下结论一致：环部分越饱和，对输精管胺摄取位点的亲和力越大，并表明药物与该摄取位点之间不存在涉及π-络合物形成的重要相互作用。
