Synthesis and Early Assessment of Epothilone‐Derived Fluorescent Probes for Microtubule Imaging

The synthesis of two bright epothilone‐based fluorescent probes for microtubule imaging is described. Building on a tested strategy for the synthesis of epothilone‐type structures, an analog of epothilone B with an extended C(6) substituent terminating in an alkyne group has been prepared. A Huisgen [3 + 2] cycloaddition of this analog with azide‐functionalized derivatives of Alexa Fluor 488 and Janelia Fluor 646 gave bright fluorescent probes emitting in the green and far‐red spectral range, respectively. Both probes bind to microtubules with high affinity and specifically label the microtubule network in A549 cells.