Synthesis and Biological Evaluation of Some New Thiophene, Thiazole, Dithiolane Derivatives and Related Compounds

A series of novel of heterocycles containing thiazole, thiophene moieties, and dithiolane derivatives were designed, synthesized, and characterized by ¹H NMR, IR, elemental analysis, and mass spectra using 2-cyanoacetylpyrrole <b>1</b> as a starting material. Under Gewald reaction condition thiazole derivative <b>3</b> was obtained while, reaction of thiocarbamoyl salt <b>6</b> with α-haloketone yielded the corresponding new synthesized derivatives <b>8</b>–<b>11</b>. When <b>1</b> was treated with cyclohydrocarbon keton in the presence of sulfur gave the corresponding aminothiophene and aminobenzothiophene derivatives <b>4</b> and <b>5</b>, respectively. Dithiolanone <b>16</b> was obtained by reaction of <b>12</b> with chloroacetyl chloride. The newly synthesized compounds were examined for their antioxidant and anticancer activities. Some of the newly synthesized compounds were found to be equipotent or more potent than drug reference as shown in the results. Moreover, molecular modeling was appreciated and was consistent with the experimental antioxidant activity results.

本研究以2-氰乙酰基吡咯（2-cyanoacetylpyrrole）化合物1为起始原料，设计并合成了一系列含噻唑、噻吩结构单元及二硫杂环戊烷衍生物的新型杂环化合物，随后通过氢核磁共振谱（¹H NMR）、红外光谱（IR）、元素分析与质谱对目标产物进行了结构表征。在格瓦德（Gewald）反应条件下，可得到噻唑衍生物3；而硫代氨基甲酰盐6与α-卤代酮发生反应，可得到相应的系列新型合成产物8~11。当化合物1与环酮在硫单质存在下反应时，可分别得到氨基噻吩衍生物4与氨基苯并噻吩衍生物5。化合物12与氯乙酰氯反应，可制得二硫杂环戊酮（dithiolanone）16。本研究对所有新合成的化合物开展了抗氧化与抗肿瘤活性评价，实验结果表明，部分新合成化合物的活性与阳性对照药物相当，甚至更优。此外，本研究还进行了分子建模（molecular modeling）研究，其结果与实验测得的抗氧化活性数据具有良好的一致性。