Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt.
Eur J Med Chem. 2009 Dec;44(12):4985-97. doi: 10.1016/j.ejmech.2009.09.002. Epub 2009 Sep 6.
The reaction of 2-oxo-N-arylpropanehydrazonoyl chlorides 3a-e with 3-methyl-2-benzofurancarboxylic acid hydrazide (7) furnished N-(aryl)propanehydrazonoyl chlorides 8a-e. X-Ray of 8c revealed the (1Z,2E) configuration of structure 8. Nucleophilic substitution reaction of 8a or 8d with piperidine resulted in the formation of 1-(piperidin-1-yl)-N(2)-arylamidrazones 9a, b. The X-ray diffraction of 9b showed its (1E,2E) configuration and it confirmed the stereoselectivity of the latter reaction. (1E,2Z,3E)-1-(Piperidin-1-yl)-1-(arylhydrazono)-2-[(3-methylbenzofuran-2-oyl)hydrazono]-4-arylbut-3-enes 11 were synthesized in stereoselective reaction from 8 or alternatively from 9. X-ray analysis of 11b showed a conversion of configuration respect to 8d or 9b. X-Ray analysis of 9b and 11b revealed the role of hydrogen interactions in the stereochemistry of their solid state structure. The in vitro antimicrobial activity of the newly synthesized compounds demonstrated an excellent growth inhibition of compounds 9 and 11 against clinically isolated strains of human fungal pathogens and exhibited a significant potency against gram-positive bacteria. Griseofulvin and Amoxicilline were used as references for antifungal and antibacterial screening. The effect of most potent antifungal compound 9b on morphological features of Aspergillus fumigatus and Candida albicans using image analyzer was studied. Furthermore, the effect of 9b on the ultra-structures of the latter fungi was occurred by transmission electron microscope.
2-氧代-N-芳基丙酰肼酰氯 3a-e 与 3-甲基-2-苯并呋喃羧酸酰肼（7）反应，生成 N-（芳基）丙酰肼酰氯 8a-e。8c 的 X 射线揭示了结构 8 的（1Z,2E）构型。8a 或 8d 与哌啶的亲核取代反应导致 1-（哌啶-1-基）-N(2)-芳基脒嗪 9a, b 的形成。9b 的 X 射线衍射显示其（1E,2E）构型，并证实了后一反应的立体选择性。（1E,2Z,3E）-1-（哌啶-1-基）-1-（芳基腙基）-2-（（3-甲基苯并呋喃-2-羰基）腙基）-4-芳基丁-3-烯 11 是通过 8 或 9 的立体选择性反应合成的。11b 的 X 射线分析显示了相对于 8d 或 9b 的构型转换。9b 和 11b 的 X 射线分析揭示了氢键在其固态结构立体化学中的作用。新合成化合物的体外抗菌活性表明，化合物 9 和 11 对临床分离的人类真菌病原体具有优异的生长抑制作用，并对革兰氏阳性菌表现出显著的效力。灰黄霉素和阿莫西林被用作抗真菌和抗菌筛选的参考。用图像分析仪研究了最有效的抗真菌化合物 9b 对烟曲霉和白色念珠菌形态特征的影响。此外，透射电子显微镜研究了 9b 对后两种真菌超微结构的影响。
