利用生物活性叠加原理,将"邻羟苯基"和"咪唑烷"分子片断有机结合,以水杨醛和乙二胺为起始原料,经缩合、NaBH_4还原制得N,N'-二邻羟苄基乙二胺(2),进而与芳醛类化合物缩合关环,合成了8种N,N'-二(2-羟苄基)取代咪唑烷类化合物(3a～3h). 化合物的结构经~1H NMR、IR、MS和元素分析等测试技术进行了表征. 结果表明,水杨醛与乙二胺的缩合反应,可专一性地生成对称双缩席夫碱化合物(1);芳醛上的取代基对缩合关环反应有显著影响,邻、对位吸电基可使芳醛的羰基活化,有利于缩合关环反应的进行,邻、对位供电基可使芳醛的羰基钝化,不利于缩合关环反应进行. 抑菌测试结果表明,质量分数为0.1%时,N,N'-二(2-羟苄基)取代咪唑烷化合物对不同菌株的抑菌活性具有明显的特异性,对白色念珠菌、大肠杆菌的抑菌率达100%.
A series of N, N'-bis (2-hydroxy benzyl) substituted imidazolidine derivatives (3a ～3h) were designd and synthesized by means of combining segments o-hydroxy phenyl and imidazolidine compounds, according to the reinforcement of biological activities. The N,N'-bis-o-hydroxy benzyl diaminoethane(2) was synthesized using salicylaldehyde and 1,2-diaminoethane, through condensation reaction and then reduction by NaBH_4, and further cyclization with aromatic aldehydes. The structures of all the compounds were confirmed by ~1H NMR, IR, mass spectra and elemental analysis. The results show that the reaction of salicylaldehyde with 1,2-diaminoethane only formed the symmetric Schiff base(1) , the condensation of aromatic aldehyde with compound 2 was noticeably different for different substituents: o-,p-substituted electron-withdrawing groups can activate aromatic aldehyde and result in a higher yield of ring closing reaction, but o- p-substitute electron-donating groups have opposite effects. The result of preliminary bioassay shows that the target compounds had obvious specificity to different bacteria at 0. 1 % (mass concentration) , and had an inhibitory rate of 100% on Monilia albican and Escherichia coli.
参考文献
| [1] | Herbert P S.FEMS Microbiology Lett[J],2001,202:1 |
| [2] | LU Jun-Rui(卢俊瑞).China Surfactant Detergent Cosmetics(日用化学工业)[J],2000,6:33 |
| [3] | Rock C O,Jackowski S.Res Commun[J],2002,292:1 155 |
| [4] | Roberts C W,McLeod R,Rice D W.Mol Biochem Parasiteology[J],2003,126:129 |
| [5] | McMurray L M,Oethinger M,Levy S B.Nature[J],1998,394:531 |
| [6] | LU Jun-Rui(卢俊瑞),MA Xia-Miao(马霞苗),LIU Mei(刘梅),YIN Ning(尹宁),CHEN Li-Ran(陈丽然),BAO Xiu-Rong(鲍秀荣).Chem J Chinese Univ(高等学校化学学报)[J],2007,28(11):2 081 |
| [7] | Perozzo R,Kuo M,Sidh A S.Biol Chem[J],2002,277:1 513 106 |
| [8] | Sharada Sivaraman,Jacque Zwahlen,Alasdair F Bell,Lizbeth Hedstrom,Peter J Tonge.Biochemistry[J],2003,42:4 406 |
| [9] | Sharada Sivaraman,Todd J Sullivan,Francis Johnson,Polina Novichenok,Guanglei Cui,Carlos Simmerling,Peter J Tonge.J Med Chem[J],2004,47:509 |
| [10] | FENG Zhi-Xiang(冯志祥),ZHANG Wan-Nian(张万年),ZHOU You-Jun(周有骏),ZHU Ju(朱驹),LV Jia-Guo(吕加国),LI Ke(李科).Acta Pharmaceutica Sin(药学学报)[J],1999,34:12 902 |
| [11] | ZHONG Wu(钟武),ZHANG Wan-Nian(张万年),LI Ke(李科),ZHOU You-Jun(周有骏),ZHU Ju(朱驹),LV Jia-Guo(吕加国).Acta Pharmaceutica Sin(药学学报)[J],1999,34:10 744 |
| [12] | ZHANG Hong(张红).Chinese J Med Chem(中国药物化学杂志)[J],1997,7(4):303 |
| [13] | LI De-Jiang(李德江),MA Wen-Zhan(马文展).Tianjin Chem Ind(天津化工)[J],2002,5:72 |
| [14] | Fromtling R A,Castaner J Voriconazole.Drugs Future[J],1996,21:3 266 |
| [15] | Helmerhost Eva J,Breeuwer Pieter,Van't HofWim.J Biol Chem[J],1999,274(11):7 286 |
| [16] | Ji H T,Zhang W N,Zhou Y J,Zhang M,Zhu J,Song Y L.J Med Chem[J],2000,43(13):2 493 |
| [17] | SHENG Chun-Quan(盛春泉),JI Hai-Tao(季海涛),ZHANG Wan-Nian(张万年).Chinese J New Drugs(中国新药杂志)[J],2002,11(4):278 |
| [18] | Patel V,Bhattacharya Pabitra K.Indian J Chem[J],Section A:Inorganic,Physical,Theoretical & Analytical;English,1984,23(6):527 |
- 下载量()
- 访问量()
- 您的评分：
-
10%
-
20%
-
30%
-
40%
-
50%