Moraski Garrett C, Franzblau Scott G, Miller Marvin J
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46656.
Heterocycles. 2010 Mar 1;80(2):977-988. doi: 10.3987/COM-09-S(S)69.
Potent antituberculosis aryl oxazoles can be made in an efficient three step process--formation of β-hydroxy amides with serine benzyl ester; cyclization to afford oxazolines; and then dehydration to give the corresponding oxazoles. Furthermore, incorporation of an appropriate aryl halide allows utilization of the Suzuki cross coupling reaction to access new chemical space and more elaborate analogs. The compounds prepared by this method were shown to possess improved activity against M. tuberculosis, extremely low toxicity toward VERO cells and, as a result, high therapeutic indexes.
强效抗结核芳基恶唑可通过高效的三步过程制备——与丝氨酸苄酯形成β-羟基酰胺;环化生成恶唑啉;然后脱水得到相应的恶唑。此外,引入合适的芳基卤化物可利用铃木交叉偶联反应进入新的化学空间并获得更精细的类似物。通过该方法制备的化合物显示出对结核分枝杆菌的活性提高、对VERO细胞的毒性极低,因此具有高治疗指数。