目的1设计合成新型四氢异喹啉类化合物,寻找具有抗真菌和抗生育双重作用的化合物,为研究具有抗真菌作用的避孕药物提供先导结构。方法:以3,4-二甲氧基苯乙胺为原料,经Pictet—Spengler反应、碱中和、取代反应、HBr裂解反应制得目标化合物并进行体外抑菌实验和杀精实验。结果:共合成14个目标化合物,它们是2-正辛烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉盐酸盐(1)、2-正壬烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉盐酸盐(2)、2-正癸烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉盐酸盐(3)、2-正十二烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉盐酸盐(4)、2-正十二烷基-6,7-二乙酰氧基-1,2,3,4-四氢异喹啉盐酸盐(5)、2-正戊烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(6)、2-正己烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(7)、2-正庚烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(8)、2-正辛烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(9)、2-正壬烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(10)、2-正癸烷基-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(11)、2-正十二烷基-6,7-二羟基-1,2,3,4-四氢异喹啉氢溴酸盐(12)、2-正十四烷基-6,7-二羟基-1,2,3,4-四氢异喹啉氢溴酸盐(13)、2-十六烷基-6,7-二羟基-1,2,3,4-四氢异喹啉氢溴酸盐(14),其中化合物5~14均未见文献报道。实验结果显示,所有目标化合物均有抗真菌活性,6个目标化合物具有抗真菌和抗生育双重作用,其中化合物11、12的活性最强。结论:发现一类具有抗真菌和抗生育双重作用的新型四氢异喹啉类化合物,为研究开发具有抗真菌活性的避孕药提供了先导结构。
Objective:To synthesize novel tetrahydroisoquinolines with both anti-fungal and contraceptive activities, so as to provide precursor structures for contraceptives with anit-fungal activities. Methods: 3,4-dimethoxyphenylethylamine was taken as the template and the title compounds were synthesized through Pictet-Spengler reaction, neutralization reaction, substitution, hydrolysis, and acylation. The anti-fungal activity and sperm-killing activity of the target compounds were tested in vitro. Results: Fourteen title compounds were obtained and they were: 2-octyl-6, 7-dimethyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrochloride(1), 2-nonyl-6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline hydrochloride (2), 2-decyl-6,7-dimethy- 1,2,3,4-tetrahydroisoquinoline hydrochloride(3), 2-dodecyl-6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline hydrochloride(4), 2-dodecyl-6,7-diacetoxy-1, 2,3,4-tetrahydro-isoquinoline hydrochloride(5 ), 2-pentyl-6,7-diacetoxy-1,2,3,4-tetrahydro-isoquinoline hydrobromide(6), 2-hexyl-6, 7-diacetoxy-1,2,3,4-tetrahydro-isoquinoline hydrobromide (7), 2-heptyl-6,7-diacetoxy-1,2,3,4-tetrahydro-isoquinoline hydrobromide (8), 2-octyl-6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline hydrobromide(9), 2-nonyl-6,7-dimethyl-1,2,3,4-tetrahydro-isoquinoline hydrobromide(10), 2-decyl-6, 7-dimethy-1,2, 3, 4-tetrahydro-isoquinoline hydrobromide ( 11 ), 2-dodecyl-6, 7-dihydroxyl-1,2, 3, 4- tetrahydro-isoquinoline hydrobromide (12), 2-tetradecyl-6, 7-dihydroxyl-1,2, 3,4-tetrahydro-isoquinoline hydrobromide (13), and 2- cetyl-6,7-dihydroxyl-1,2,3,4-tetrahydro-isoquinoline hydrobromide(14). Compounds 5-14 were firstly reported. It was found that all the 14 compounds had anti-fungal activity and 6 compounds also showed sperm-killing activities, with compounds 11,12 having the strongest activities. Conclusion: A group of novel compounds with both anti-fungal and contraceptive activities have been synthesized, which provide a precursor structure for developing new contr