Green approach for synthesis of bioactive Hantzsch 1,4-dihydropyridine derivatives based on thiophene moiety via multicomponent reaction

A novel green and efficient one-pot multicomponent reaction of dihydropyridine derivatives was reported as having good to excellent yield. In the presence of the catalyst ceric ammonium nitrate (CAN), different 1,3-diones and same starting materials as 5-bromothiophene-2-carboxaldehyde and ammonium acetate were used at room temperature under solvent-free condition for the Hantzsch pyridine synthesis within a short period of time. All compounds were evaluated for their in vitro antibacterial and antifungal activity and, interestingly, we found that 5(b–f) show excellent activity compared with Ampicillin, whereas only the 5e compound shows excellent antifungal activity against Candida albicans compared with griseofulvin. The cytotoxicity of all compounds has been assessed against breast tumour cell lines (BT-549), but no activity was found. The X-ray structure of one such compound, 5a, viewed as a colourless block crystal, corresponded accurately to a primitive monoclinic cell.

本研究报道了一种新颖、绿色高效的二氢吡啶类衍生物多组分一锅法合成工艺，该工艺可获得良好至优异的反应收率。该反应以硝酸铈铵（ceric ammonium nitrate, CAN）为催化剂，以不同的1,3-二酮类化合物，搭配固定起始原料5-溴噻吩-2-甲醛与乙酸铵为反应底物，在室温无溶剂条件下快速完成汉奇吡啶（Hantzsch pyridine）合成反应。对所有合成产物开展了体外抗菌与抗真菌活性评价，结果显示，相较于氨苄西林（Ampicillin），化合物5(b~f)均表现出优异的抗菌活性；而相较于灰黄霉素（griseofulvin），仅化合物5e对白色念珠菌（Candida albicans）展现出优异的抗真菌活性。此外，针对所有化合物开展了BT-549乳腺癌细胞系的细胞毒性评价，未检测到相关活性。对其中化合物5a的X射线晶体结构进行解析，该化合物为无色块状晶体，其晶胞参数与原始单斜晶胞完全吻合。