Exploration of the labeling of [11C]tubastatin A at the hydroxamic acid site with [11C]carbon monoxide

We aimed to label tubastatin A (1) with carbon-11 (t(1/2)=20.4min) in the hydroxamic acid site to provide a potential radiotracer for imaging histone deacetylase 6 in vivo with positron emission tomography. Initial attempts at a one-pot Pd-mediated insertion of [C-11]carbon monoxide between the aryl iodide (2) and hydroxylamine gave low radiochemical yields (<5%) of [C-11]1. Labeling was achieved in useful radiochemical yields (16.1 +/- 5.6%, n=4) through a two-step process based on Pd-mediated insertion of [C-11]carbon monoxide between the aryl iodide (2) and p-nitrophenol to give the [C-11]p-nitrophenyl ester ([C-11]5), followed by ultrasound-assisted hydroxyaminolysis of the activated ester with excess hydroxylamine in a DMSO/THF mixture in the presence of a strong phosphazene base P-1-t-Bu. However, success in labeling the hydroxamic acid group of [C-11]tubastatin A was not transferable to the labeling of three other model hydroxamic acids.