Synthesis and cytotoxicity evaluation of diastereoisomers and N-terminal analogues of Tubulysin-U

Sreejith P. Shankar, Serena Bigotti, Paolo Lazzari, Ilaria Manca, Marco Spiga, Monica Sani, Matteo Zanda

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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 languageEnglish
Pages (from-to)6137-6141
Number of pages5
JournalTetrahedron Letters
Volume54
Issue number45
Early online date11 Sep 2013
DOIs
Publication statusPublished - 6 Nov 2013

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Keywords

  • tubulysin
  • diastereoisomers
  • structure–activity-relationship
  • cytotoxicity
  • anti-cancer

Cite this

Shankar, S. P., Bigotti, S., Lazzari, P., Manca, I., Spiga, M., Sani, M., & Zanda, M. (2013). Synthesis and cytotoxicity evaluation of diastereoisomers and N-terminal analogues of Tubulysin-U. Tetrahedron Letters, 54(45), 6137-6141. https://doi.org/10.1016/j.tetlet.2013.09.010