Epothilone D and its 9-Methyl analogues: combinatorial syntheses, conformation, and biological activities

  • Eur J Med Chem. 2013 Oct:68:321-32. doi: 10.1016/j.ejmech.2013.08.003.
Feng Sang  1 ,  Peng Feng ,  Jie Chen ,  Yahui Ding ,  Xiyan Duan ,  Jiadai Zhai ,  Xiaoyan Ma ,  Bin Zhang ,  Quan Zhang ,  Jianping Lin ,  Yue Chen
Affiliations
  • 1. State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, PR China.
PMID: 23994325 DOI: 10.1016/j.ejmech.2013.08.003
Abstract

Epothilone D (Epo D) and its 9-Methyl conformational analogues were synthesized through a highly efficient combinatorial approach. The fragment E was synthesized in 11 total steps with 6 longest linear steps, and each aldehyde B was prepared via a 3-step sequence. Starting from the common precursor E and a suitable aldehydes B, each target molecule were obtained in only 4 steps. The 9-(S)-epo D and 9-(R)-epo D demonstrated significant difference in inhibition activities against Cancer cell lines and in conformational analysis.

Keywords
Analogues; Bioactivity; Epothilone; Structure activity relationship; Total synthesis.