1960 年 80 巻 1 号 p. 1-6
The method of Grewe and others for synthesis of 10-hydroxydecahydroisoquinoline requires several steps for formation of the skeletal structure and is poor in yield, while that of Mannich and others for 4-substituted derivative is limited to formation of N-benzyl compound and cannot be used for synthesis of N-methyl derivatives which are pharmacologically valuable. Studies were carried out in order to prepare 4-substituted derivatives of 2-methyl-10-hydroxydecahydroisoquinoline, known as an analgesic, and a new process illustrated in Chart 1 was found. This new synthetic method is a combination of the Mannich reaction and the subsequent aldol condensation-type cyclization. The procedure is very simple and the product is obtained in good yield. 2-Methyl-4-anisoyl-10-hydroxydecahydroisoquinoline was first prepared by this method and the two kinds of isomer produced during this reaction were separated by the difference in their solubility in chloroform. Examinations were then made on the properties of each isomer, their isomerization, and the relationship between reaction conditions and formation ratio of isomers.