Xia Likai, Idhayadhulla Akber, Lee Yong Rok, Kim Sung Hong, Wee Young-Jung
School of Chemical Engineering, Yeungnam University , Gyeongsan 712-749, Republic of Korea.
ACS Comb Sci. 2014 Jul 14;16(7):333-41. doi: 10.1021/co500002s. Epub 2014 May 2.
With the aim of developing a general and practical method for library production, a novel and efficient two-phase microwave-assisted cascade reaction between isatins and β-ketoamides in [Bmim]BF4/toluene was developed for the synthesis of pyrrolo[3,4-c]quinoline-1,3-diones. The features of this methodology are, the use of microwave-assisted rapid synthesis, mild reaction conditions, high yields, operational simplicity, facile product separation, and recyclability. Furthermore, the antibacterial activities of the pyrrolo[3,4-c]quinoline-1,3-dione derivatives produced were evaluated against Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Enterobacter aerogenes) and Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus). These derivatives showed antibacterial activities against Gram-positive strains that were at least equivalent to that against Gram-negative strains. Compound 7{3,5} displayed the most potent antibacterial activity against P. aeruginosa (MIC = 0.5 μg/mL) and greater activity than standard ampicillin (MIC = 1 μg/mL). Compound 7{4,7} exhibited the best inhibitory activity against E. coli and E. aerogenes (MIC = 1 and 0.5 μg/mL), compared with the standard ampicillin (both MICs = 1 μg/mL). The synthesized pyrrolo[3,4-c]quinoline-1,3-diones are expected to be widely used as lead compounds for the development of new antibacterial agents.
为了开发一种通用且实用的库制备方法，我们在[Bmim]BF4/甲苯体系中，开发了一种新颖高效的靛红与β-酮酰胺之间的两相微波辅助级联反应，用于合成吡咯并[3,4-c]喹啉-1,3-二酮。该方法的特点包括：采用微波辅助快速合成、反应条件温和、产率高、操作简便、产物分离容易以及可循环利用。此外，还评估了所制备的吡咯并[3,4-c]喹啉-1,3-二酮衍生物对革兰氏阴性菌（大肠杆菌、铜绿假单胞菌和产气肠杆菌）和革兰氏阳性菌（蜡样芽孢杆菌和金黄色葡萄球菌）的抗菌活性。这些衍生物对革兰氏阳性菌株的抗菌活性至少与对革兰氏阴性菌株的相当。化合物7{3,5}对铜绿假单胞菌表现出最强的抗菌活性（MIC = ０.５μg/mL），且活性高于标准氨苄西林（MIC = 1μg/mL）。与标准氨苄西林（两者MIC均为1μg/mL）相比，化合物7{4,7}对大肠杆菌和产气肠杆菌表现出最佳的抑制活性（MIC分别为1和0.5μg/mL）。所合成的吡咯并[3,4-c]喹啉-1,3-二酮有望作为新型抗菌剂开发的先导化合物被广泛应用。
