Total Synthesis of N14-Desacetoxytubulysin H
journal contributionposted on 12.04.2007, 00:00 by Peter Wipf, Zhiyong Wang
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.