A straightforward click-approach towards pretubulysin-analogues

Abstract

The [3+2]-cycloaddition of an azido tripeptide, corresponding to the left hand side of pretubulysin, with a range of alkynes, such as propiolic acid amides and propargyl ethers, allows the straightforward syntheses of libraries of tubulysin derivatives. Via this click approach, a chimera of pretubulysin and dolastatin 10, both highly potent antimitotic drug candidates, also becomes accessible.