Synthesis and biological evaluation of tubulysin D analogs related to stereoisomers of tubuvaline

Exploratory Research Laboratories, Kyorin Pharmaceutical Co Ltd, 2399-1 Nogi, Nogi-Machi, Shimotsuga-Gun, Tochigi 329-0114, Japan.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.33). 01/2011; 21(1):431-4. DOI: 10.1016/j.bmcl.2010.10.118
Source: PubMed

ABSTRACT The synthesis and biological evaluation of stereoisomers in tubulysin D are described. The stereoselective synthesis of all possible stereoisomers of C-11 and C-13 positions in tubulysin D was achieved by employing 1'-epi-Tuv-Me, 3'-epi-Tuv-Me, and ent-Tuv-Me and their biological properties were evaluated. It is clear that the stereochemistries of the C-11 and C-13 positions in tubulysin D have no practical impact on the inhibition of tubulin polymerization but play a role in the potent antiproliferative activities.