Department of Chemistry and Biochemistry, Arizona State University , P.O. Box 871604, Tempe, Arizona 85287-1604, United States.
J Nat Prod. 2014 Apr 25;77(4):863-72. doi: 10.1021/np400947d. Epub 2014 Apr 2.
The lupane-type triterpene betulin (1) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence 7→11→12 was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the 11 and 13/14→17 conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer 12 and intermediate 25 are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for 4, 8, 9, 15/16, 19, 20, 24, and 26, which further defines the utility of the betulin scaffold.
五环三萜白桦脂烷型化合物 betulin（1） 经过一系列结构修饰，用于评估其对癌细胞生长的抑制活性。反应序列 7→11→12 特别值得注意，因为它提供了一个白桦脂烷衍生的胺二聚体。其他意想不到的合成结果包括 11 和 13/14→17 的转化，得到了一个咪唑衍生物。报道了二聚体 12 和中间体 25 的 X 射线晶体结构。所有白桦脂烷修饰物都进行了抗癌活性测试，针对 P388 鼠和人细胞系。发现 4、8、9、15/16、19、20、24 和 26 对癌细胞生长有显著抑制作用，这进一步证实了白桦脂烷支架的实用性。
