The effect of vindoline C-16 substituents on the biomimetic coupling reaction: synthesis and cytotoxicity evaluation of the corresponding vinorelbine analogues

  • Bioorg Med Chem Lett. 2012 May 15;22(10):3485-7. doi: 10.1016/j.bmcl.2012.03.082.
Weibin Song  1 ,  Lingjun Hu ,  Yuhui Meng ,  Lei Ma ,  Dean Guo ,  Xuan Liu ,  Lihong Hu
Affiliations
  • 1. Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
PMID: 22525316 DOI: 10.1016/j.bmcl.2012.03.082
Abstract

A new series of vinorelbine analogues are designed and synthesized to explore the vindoline C-16 substituent effects on the biomimetic coupling with catharanthine, and the structure-activity relationships of these vinorelbine analogues as cytotoxic agents are also studied. The results show that introduction of severe steric hindrance and/or electron-withdrawing group at C-16 site are not propitious to improving the yields of the coupling reaction, and the SAR information collected so far suggests that small alkyl groups substituted at C-16 of vindoline are conductive to maintaining the cytotoxicity.