Total synthesis of N14-desacetoxytubulysin H

Org Lett. 2007 Apr 12;9(8):1605-7. doi: 10.1021/ol070415q. Epub 2007 Mar 17.


[reaction: see text] The N14-desacetoxy analogue of tubulysin H was prepared in 20 steps and 2.1% overall yield. Our strategy features a thiazole anion addition to assemble the tubuvaline residue at the C(10)-C(11) bond, as well as acylations at N5, N14, and N17. This iterative coupling approach, as well as the removal of the labile N,O-acetal at N14, enables the synthesis of analogues for detailed studies of structure-activity relationships in this family of potent tubulin disrupters.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Molecular Structure
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Organic Chemicals / chemical synthesis*
  • Organic Chemicals / chemistry


  • N14-desacetoxytubulysin H
  • Oligopeptides
  • Organic Chemicals