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

Feng Sang; Peng Feng; Jie Chen; Yahui Ding; Xiyan Duan; Jiadai Zhai; Xiaoyan Ma; Bin Zhang; Quan Zhang; Jianping Lin; Yue Chen

doi:10.1016/j.ejmech.2013.08.003

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. Epub 2013 Aug 11.

Authors

Feng Sang¹, Peng Feng, Jie Chen, Yahui Ding, Xiyan Duan, Jiadai Zhai, Xiaoyan Ma, Bin Zhang, Quan Zhang, Jianping Lin, Yue Chen

Affiliation

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Breast Neoplasms / drug therapy*
Cell Line, Tumor
Cell Proliferation / drug effects
Combinatorial Chemistry Techniques
Computer Simulation
Crystallography, X-Ray
Epothilones* / chemical synthesis
Epothilones* / chemistry
Epothilones* / pharmacology
Female
Humans
Inhibitory Concentration 50
Models, Biological
Molecular Structure

Substances

Antineoplastic Agents
Epothilones
desoxyepothilone B