6，7，10-三甲氧基二苯并[f，h]四氢异喹啉的合成以及碘化亚铜催化的三组分偶联反应
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摘要
娃儿藤生物碱(tylophora alkaloids)具有抗炎、抗病毒以及抗肿瘤等多种生理活性,近年来受到有机化学和药物化学研究者的关注,在合成方法、活性评价以及作用机制等方面取得了令人瞩目的成果。本文第一章在参考已有的娃儿藤生物碱构效关系研究成果基础上,设计了一种新的娃儿藤生物碱衍生物6,7,10-三甲氧基二苯并[f,h]四氢异喹啉101。用β-丙氨酸作为初始原料,先将β-丙氨酸与对甲氧基苯乙酰氯反应,然后经过酰基化、分子内缩合、氧化偶联反应得到目标分子的前体化合物107。今后的工作将围绕化合物107的还原以及系列衍生物的制备和活性评价展开。
含氮杂环取代的二芳基醚类化合物往往具有较高的生物活性、更低的毒性,在农药、医药等工业上有着广泛的应用。本文第二章在本组的最新研究成果的基础上,采用CuI/ N,N-二甲基甘氨酸的催化体系,通过对溴碘苯、含氮杂环、酚的三组分偶联反应成功合成了含氮杂环取代的二芳醚类化合物。在模板反应中,我们用对溴碘苯、咪唑、苯酚作底物,借鉴同组结果优化出最佳反应条件:10 mol% CuI,20 mol% N,N-二甲基甘氨酸,K3PO4为碱,DMSO为溶剂。然后,对其他含氮杂环苯并咪唑、三氮唑和其他取代酚进行了研究,取得了较好的产率。但强吸电子基取代的酚的反应则不尽人意。总之,该反应为合成含氮杂环取代的二芳基醚类化合物提供一种高效、绿色的方法。
Much attention has been played to tylophora alkaloids due to their biological properties, such as antitumor and antifungal activities. Therefore, a lot of their derivatives have been synthesized and evaluated in recent years. In the first chapter of this dissertation, based on the achievements about the structure-activity relationship of tylophora alkaloids, a new kind of derivatives was proposed. One derivative named 6,7,10-trimethoxy- dibenzo[f,h]isoquinoline was tried fromβ-alanine by 5 steps. In the future, the target molecular and its analogues will be prepared.
Nitrogen-containing heteocyclic substituted diaryl ethers, widely applied in the field of pepstides, have been shown to be high active with lower toxicity. In the second chapter of this dissertation, a three component coupling reaction was developed to prepare this kind of diaryl ethers for the first time, based on the latest work in our group. Initially, 4-bromphenyl iodide, imidazole and phenol were used and the reaction condition was optimized as follows: 10 mol% CuI, 20 mol% N,N-dimethylglycine, using K3PO4 as the base and DMSO as the solvent. Under these conditions, many substrates tried could be transformed into the desired products in moderate to good yields. Regretfully, phenols bearing strong electron-withdrawing groups were unfavorable. In short, an efficient and green method was provided for above diaryl ethers.
含氮杂环取代的二芳基醚类化合物往往具有较高的生物活性、更低的毒性,在农药、医药等工业上有着广泛的应用。本文第二章在本组的最新研究成果的基础上,采用CuI/ N,N-二甲基甘氨酸的催化体系,通过对溴碘苯、含氮杂环、酚的三组分偶联反应成功合成了含氮杂环取代的二芳醚类化合物。在模板反应中,我们用对溴碘苯、咪唑、苯酚作底物,借鉴同组结果优化出最佳反应条件:10 mol% CuI,20 mol% N,N-二甲基甘氨酸,K3PO4为碱,DMSO为溶剂。然后,对其他含氮杂环苯并咪唑、三氮唑和其他取代酚进行了研究,取得了较好的产率。但强吸电子基取代的酚的反应则不尽人意。总之,该反应为合成含氮杂环取代的二芳基醚类化合物提供一种高效、绿色的方法。
Much attention has been played to tylophora alkaloids due to their biological properties, such as antitumor and antifungal activities. Therefore, a lot of their derivatives have been synthesized and evaluated in recent years. In the first chapter of this dissertation, based on the achievements about the structure-activity relationship of tylophora alkaloids, a new kind of derivatives was proposed. One derivative named 6,7,10-trimethoxy- dibenzo[f,h]isoquinoline was tried fromβ-alanine by 5 steps. In the future, the target molecular and its analogues will be prepared.
Nitrogen-containing heteocyclic substituted diaryl ethers, widely applied in the field of pepstides, have been shown to be high active with lower toxicity. In the second chapter of this dissertation, a three component coupling reaction was developed to prepare this kind of diaryl ethers for the first time, based on the latest work in our group. Initially, 4-bromphenyl iodide, imidazole and phenol were used and the reaction condition was optimized as follows: 10 mol% CuI, 20 mol% N,N-dimethylglycine, using K3PO4 as the base and DMSO as the solvent. Under these conditions, many substrates tried could be transformed into the desired products in moderate to good yields. Regretfully, phenols bearing strong electron-withdrawing groups were unfavorable. In short, an efficient and green method was provided for above diaryl ethers.
引文
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