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| 新型四氢异喹啉类化合物的合成及其抗真菌和抗生育活性研究? |
| 吕加国,周有骏,朱驹,姜远英,郑灿辉,曹永兵,李耀武,蒋庆锋,梁蓉梅 |
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| (第二军医大学药学院药物化学教研室, 上海,200433) |
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| 摘要: |
| 目的：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。 |
| 关键词: 四氢异喹啉类 抗真菌药 避孕药? |
| DOI：10.3724/SP.J.1008.2006.01304 |
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| 基金项目: |
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| Synthesis of novel tetrahydroisoquinolines and study of their anti-fungal and contraceptive activities? |
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| Abstract: |
| 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-tetrahydro-isoquinoline 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 contraceptives with anti-fungal activities. |
| Key words: tetrahydroisoquinolines antifungal agents contraceptives? |
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