Synthesis,crystal structures and antifungal activity of novel triazole compounds containing 1,3-dioxolane
-
摘要: 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。
-
关键词:
- 1,3-二氧戊环类化合物 /
- 合成 /
- 晶体结构 /
- 抗真菌活性
Abstract: 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.-
Key words:
- 1,3-dioxolane /
- synthesis /
- crystal structure /
- antifungal activity
-
[1] Koltin,Y,Hitchcock CA.The search for new triazole antifungal agents[J].Curr Opin Chem Biol,1997,1(2):176. [2] 陈平.抗真菌药物的不良反应[J].医师进修杂志,2005,28(11):12. [3] Plempel M. Experience,recognitions and questions in azole antimycotics[J]. Jpn Med Mycol,1982,23 (1):17. [4] Wilkinson CF,Krystyna H. Structure-activity relationships in the effects of 1-alkylimidazoles on microsomal oxidation in vitro and in vivo[J].Biochem Pharmacol,1974,23 (17):2377. [5] Chai XY,Zhang J,Yu SC,et al.Design,synthesis,and biological evaluation of novel 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamin-2-propanols[J].Bioorg Med Chem Lett,2009,19(6):1811. [6] 吴义杰,周旭,张大志,等.三唑类化合物的合成及其抗真菌活性Ⅱ[J]. 中国药物化学杂志,1998,8(4):235. [7] Shi W, Nacev BA,Bhat S,et al.Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal Activities of Itraconazole[J]. ACS Med Chem Lett,2010,1:155. [8] Saksena AK,Cooper AB,Guzik H,et al.2,4,4,4-tetra substituted-1,3-dioxolane compounds[P].US,WO 88/05048,1988-07-14. [9] Camps P,Farrés X,García Ma L,et al.Steroselective syntheses of (+)-and (-)- terconazole[J].Tetrahedron:Asymmetry,1995,6(9):2365. [10] National Committee for Clinical Laboratory Standards.Reference method for broth dilution antifungal susceptibility testing of yeast,Approved standard.Document M27-A3[S].PA:Wayne:2009. [11] National Committee for Clinical Laboratory Standards.Reference method for broth dilution antifungal susceptibility testing of yeast,Approved Standard.Document M38-A2[S]. PA:Wayne:2008. -
点击查看大图
计量
- 文章访问数: 5228
- HTML全文浏览量: 354
- PDF下载量: 349
- 被引次数: 0
下载:
