药物化学  >> Vol. 2 No. 2 (May 2014)

Erythribyssin H类似物的设计与合成
Design and Synthesis of the Derivative of Erythribyssin H

DOI: 10.12677/HJMCe.2014.22003, PDF, HTML, 下载: 2,414  浏览: 7,865 

作者: 王亚楼, 唐文婧, 巫 凯:中国药科大学药物化学教研室,南京

关键词: 2-(4-羟基-35-二甲氧基苯基)-6-羟基苯并呋喃Erythribyssin H类似物Vilsmier-Schmidet反应交叉McMurry偶联反应合成 2-(4-Hydroxy-35-dimethoxyphenyl)-6-hydroxybenzofuran Erythribyssin H Derivative Vilsmier-Schmidet Reaction Cross Mcmurry Coupling Reaction Synthesis

摘要: 目的:提供合成Erythribyssin H类似物(2)的路线。方法:以间苯二酚和丁香醛为起始原料,经Vilsmier- schmidet反应和酚羟基保护反应合成2-羟基4-苄氧基苯甲醛(4)3,5-二甲氧基4-苄氧基苯甲醛(5)。然后使用McMurry交叉偶联反应得到邻乙烯基苯酚产物(6)6I2/K2CO3试剂作用下环合并脱保护成为Erythribyssin H类似物(2)。结果:目标化合物和相应的中间体的化学结构都经过1H-NMRIRMS确证。结论:以间苯二酚和丁香醛为起始原料经McMurry交叉偶联反应合成了Erythribyssin H类似物(2),该合成路线简单,易于操作,(2)的总收率为31%
Abstract: Objective: To develop a synthetic route for Erythribyssin H derivative. Methods: 2-(4-Hydroxy-3, 5-dimethoxyphenyl)-6-hydroxybenzofuran (Erythribyssin H derivative, compound 2) can be synthesized from resorcinol and syringaldehyde by Vilsmier-schmidet reaction to get two key intermediates 4-benzyloxyl-2-hydroxybenzaldehyde (compound 4) and 3,5-dimethoxy-4-benzyloxyl- benzaldehyde (compound 5). Then via McMurry coupling reaction the two intermediate products developed to be cross coupling product 5-(benzyloxy)-2-(4-(benzyloxy)-3,5-dimethox-ysty-ryl)- phenol (compound 6). The product went through oxidative cyclization reaction, deprotective reaction, finally developed to be the derivative of Erythribyssin H(2). Results: The structure of all products was confirmed by 1H-NMR, IR and MS analysis. Conclusion: Erythribyssin H derivative was synthesized from resorcinol and syringaldehyde via McMurry coupling reaction, which is easy to conduct, and the overall yield is 31%.

文章引用: 王亚楼, 唐文婧, 巫凯. Erythribyssin H类似物的设计与合成[J]. 药物化学, 2014, 2(2): 14-19. http://dx.doi.org/10.12677/HJMCe.2014.22003

参考文献

[1] 胡淑国, 宋光耀 (2009) 腺苷酸活化蛋白激酶与胰岛素抵抗. 国际内科学杂志, 3, 137-140.
[2] Nguyen, P.H., Nguyen, T.N.A., Dao, T.T., et al. (2010) AMP-Activated protein kinase (AMPK) activation by benzofurans and coumestans isolated from Erythrina abyssinica. Journal of Natural Products, 4, 598-602.
[3] Duan, X.F., Zeng, J., Lu, J.W., et al. (2006) Insights into the general and efficient cross McMurry reactions between ketones. The Journal of Organic Chemistry, 71, 9873-9875.
[4] Nenitzescu, C.D. and Isacescu, D. (1931) Reactions catalyzed by metallic halides. II. Mechanism of the Friedel-Crafts reaction. Justus Liebigs Annalen der Chemie, 491, 210-220.
[5] Wilford, L.M. and Stuart, H. (1996) Preparation of 2,4-dihydroxybenzaldehyde by the Vilsmeier-Haack reaction. Synthetic Communications, 26, 603-610.
[6] Dewick, P.M. (1981) Benzyl p-toluenesulphonate as an 0-benzylating agent for the protection of phenols. Synthetic Communications, 11, 853-857.
[7] Daly, J., Homer, L. and Witkop, B. (1961) Chemical and enzymatic routes to methoxydopamines. Journal of the American Chemical Society, 83, 4787-4792.
[8] Wilford, L.M., Monica, H. and Jack, D. (1996) The regioselective 4-benzylation of 2,4-dihydroxybenzaldehyde. Synthetic Communications, 26, 593-601.
[9] Suchitra, B., Kshama, R. and Sandip, K.N. (2010) Efficient one-pot synthesis of 2-arylbenzo[b]furans from 2-styrylphenols using CuBr2. Synthetic Communications, 40, 2736-2746.