新型三唑二氧戊环类化合物的合成、晶体结构及抗真菌活性

Synthesis,crystal structures and antifungal activity of novel triazole compounds containing 1,3-dioxolane

目的合成(E)1-[4-(2,4-二氟苯基)-2-[2-(4-氟苯基)-乙烯基]-[1,3]二氧戊环-4-甲基]-1H-[1,2,4]三氮唑化合物的几何异构体,测定其晶体结构,并考察其体外抗真菌活性。方法以间二氟苯为起始原料,经Friedel-Crafts反应、与三氮唑缩合、环氧化,得到中间体1-[2-(2,4-二氟苯基)-2,3-环氧丙基]-1H-1,2,4-三唑甲磺酸盐,将环氧化物甲烷磺酸盐水解,然后与对氟肉桂醛缩合脱水制得目标化合物6 Ka和6 Kb,经1H NMR、MS和X-射线单晶衍射测定结构,并测试其体外抗真菌活性。结果 6 Ka属单斜晶系,空间群P2(1)/c,为顺式构型。6Kb属单斜晶系,空间群P2(1)/n,为反式构型。目标化合物对5种致病真菌在体外均有很强的抑菌活性。化合物6 Kb的抑菌活性优于化合物6Ka。结论该类型反式构型化合物的体外抗真菌活性优于其顺式构型。

Objective To synthesize the geometric isomer of（E）-1-（（4-（2,4-difluorophenyl）-2-（4-fluorostyryl）-1,3-dioxolan-4-yl）methyl）-1H-1,2,4-triazole,determine their structures by XRD and evaluate their antifungal activities in vitro.Methods The target compounds were prepared from 1H-1,2,4-triazole and 2-chloro-2′,4′-difluoroacetophenone,the key oxirane intermediate was obtained by Corey-Chaykov-asky epoxidation.The key oxirane intermediate was hydrolyzed in the presence of 9% sulphuric acid,then the product was reacted with 4-Fluorocinnamaldehyde by condensation reaction to afford 6Ka and 6Kb.Their structures were charact-erized by 1H NMR,MS and XRD.Results Compound 6Ka belonged to monoclinic crystal system,space group P2（1）/c and had a cis configuration.While Compound 6Kb belonged to monoclinic crystal system,space group P2（1）/n and had a trans configuration.Both compounds which showed strong antifungal activities in vitro against five fungis.The antifungal activities of compound 6Kb was better than that of 6Ka.Conclusion The trans configuration of this kind had a predominant in vitro antifungal activities than the corresponding cis configuration.