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

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. A highly efficient combinatorial approach was applied to synthesize epothilone D and its 9-Methyl analogues. [Display omitted] •A highly efficient approach was applied to synthesize Epo D and its new analogues.•The new analogues demonstrated significant difference in biological activity.•The conformations of Epo D and its new analogues were investigated.