Total synthesis of N14-desacetoxytubulysin H.
[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.
Wipf
Peter
P
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. pwipf+@pitt.edu
Wang
Zhiyong
Z
D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D009930:Organic Chemicals / Q000138:chemical synthesis* / Q000737:chemistry
C520247:N14-desacetoxytubulysin H; D009842:Oligopeptides; D009930:Organic Chemicals