鎭痛剤としてのHydro化Quinoline類及びIsoquinoline類の合成研究 (第2報)

2-Methyl-9-ethoxycarbonyldecahydroisoquinolineの合成

抄録

The preparation of 2-methyl-9-ethoxycarbonyldecahydroisoquinoline was carried out by the application of the Robinson cyclization. The condensation of 1-diethylamino-3-butanone methiodide with 1-methyl-3-ethoxycarbonyl-4-piperidone yielded 2-methyl-6-oxo-9-ethoxy carbonyl-Δ^{5, 10}-octahydroisoquinoline (III, R=H). Hydrogenation of (III) in the presence of the Adams' platinum catalyst yielded 2-methyl-6-hydroxy-9-ethoxycarbonyldecahydroisoquinoline (IV), which, on selective oxidation with activated manganese dioxide, gave 2-methyl-6-oxo-9-ethoxycarbonyldecahydroisoquinoline (VI). Reaction of (VI) with ethylenethioglycol formed a thioketal with a characteristic odor. This thioketal was converted to 2-methyl-9-ethoxycarbonyldecahydroisoquinoline (VIII) by refluxing with Raney nickel in ethanol. 2-Methyldecahydroisoquinoline-9-carboxylic acid lactone-6 (V) was prepared by reacting 2-methyl-9-ethoxycarbonyl-6-hydroxydecahydroisoquinoline (IV) in benzene with hydrochloric acid gas. Pharmacological tests showed that (III, R=H) and (V) possessed activities 1/25 to 1/30 of that of morphine, while (VI) and (VIII) showed only a slight activity.