Abstract
Tubulysins are potent anti-mitotic natural compounds and a scalable and efficient synthetic route for generation of its analogues has been developed and extended to the synthesis of diastereoisomers and N-terminal analogues of tubulysin-U. Structure–activity-relationship studies on these synthetic analogues reaffirmed the significance of native stereochemistry of tubulysins for optimal biological activity and cytotoxicity. However, while modification of Tup stereochemistry has only minor effect on the tubulysins cytotoxicity, Tuv stereochemistry is critically important and modification of either Tuv stereocentre produced a dramatic drop in cytotoxicity.
Original language | English |
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Pages (from-to) | 6137-6141 |
Number of pages | 5 |
Journal | Tetrahedron Letters |
Volume | 54 |
Issue number | 45 |
Early online date | 11 Sept 2013 |
DOIs | |
Publication status | Published - 6 Nov 2013 |
Keywords
- tubulysin
- diastereoisomers
- structure–activity-relationship
- cytotoxicity
- anti-cancer