含二茂铁基Schiff碱类化合物的设计、合成及抗真菌活性研究  

Design,synthesis and antifungal activity of ferrocene Schiff base

作　　者：李文昭[1] 梁振[1] 郭梦笔 李硕[1] 刘薇[1] 郭春[1] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《中国药物化学杂志》2015年第6期430-435,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家基础科学人才培养基金项目(J1103606)

摘　　要：目的合成一系列含二茂铁基的Schiff碱类化合物,并测定其体外抗真菌活性。方法以二茂铁为起始原料,经乙酰化、氧化、酰化、肼解制得中间体二茂铁甲酰肼(1);以各种4-取代的苯硫酚和3-氯丙酸为起始原料,经取代、环合制得中间体取代2H-苯并[b]噻喃-4-酮(2a);以取代苯酚和3-氯丙酸为起始原料,经加成、环合制得中间体取代2H-苯并[b]吡喃-4-酮(2b);以各种取代苯胺和丙烯酸为起始原料,经加成、环合制得中间体取代2,3-二氢喹啉-4(1H)-酮(2c),中间体2a、2b、2c分别与1反应得到目标化合物。采用二倍浓度稀释法测试各目标化合物的体外抗真菌活性。结果与结论合成的15个化合物均未见文献报道,其结构经1H-NM R、HRM S谱确证;活性测试结果表明,多个目标化合物对测试真菌表现出一定的体外抑菌活性。A series of compounds containing ferrocene Schiff base were designed and synthesized, and the primary antifungal activities of the compounds had been screened. Ferrocene was used as starting material, acetylferrocene, ferrocenecarboxylic acid; ferrocene carbonyl chloride; ferrocene hydrazide were formed in turn. Thiochromanones were synthesized by thiophenols and 3-chloropropionic acid through addition and cy- clization reactions; chroman4-ones were synthesized by phenols and 3-chloropropionic acid through addition and cyclization reactions ;2,3-dihydro quinoline-4-ketones were synthesized by phenylamines and crylic acid through addition and cyclization reactions. And target compounds were combined by these intermediates and ferrocene hydrazide. The antifungal activities of target compounds were tested in vitro against 6 kinds of common clinical fungi with fluconazol and voriconazole as control drugs by using two-fold dilution method. Fifteen compounds which have not been reported in literature were designed and synthesized. Their structures of compounds were confirmed by MS and 1H-NMR. The preliminary results showed that most compounds had antifungal activities in different levels.

关 键 词：二茂铁 SCHIFF碱 合成 抗真菌活性 

分 类 号：R914.5[医药卫生—药物化学]