Tritiation of azido-labeled diiodo cabazitaxel (Jevtana) and docetaxel (Taxotere) derivatives to generate 3 H-photoaffinity probes

Abstract

Radiolabelled azidophenyl analogues can make powerful photoaffinity probes for the identification of molecular targets. We describe our efforts to prepare tritiated azidophenyl analogues of the taxols cabazitaxel and docetaxel. Late-stage tritiation by isotope exchange with diiodo precursors resulted in reduction of the azide moiety, which could only be overcome by addition of high excess of a sacrificial azide. Iodine-deuterium exchange experiments on a model system established that deiodination with concomitant azide reduction is a general problem when performing such isotope-exchange reactions on azide-containing aryl iodides.

Keywords: I-D exchange; I-T exchange; azide reduction; cabazitaxel; docetaxel; photoaffinity probes; tritium-labeling.