Synthesis of [11C](-)-α,α-dideutero-phenylephrine for in vivo kinetic isotope studies

(-)-[11C]Phenylephrine and positron emission tomography could potentially be used to assess neuronal monoamine oxidase activity in the heart. Previous data for (-)-[11C]phenylephrine indicate that, although its retention and neuronal selectivity parallel that of the neuronal mapping agent (-)-[11C]hydroxyephedrine, its neuronal storage and clearance properties are quite different. In order to study the in vivo kinetics of (-)-[11C]phenylephrine in greater detail, the dideutero analog [11C]-(-)-α,α-dideutero-phenylephrine. 1, was synthesized by [11C]methylation of the precursor (-)-α,α-dideutero-m-octopamine. The key step in the procedure was BD3 reduction of the cyanohydrin derived from 3-hydroxybenzaldehyde. Deuterium incorporation at the alpha positions of m-octopamine was confirmed by NMR and mass spectroscopy of the deuterated product and by comparison of spectral data with undeuterated m-octopamine. (-)-α,α-Dideutero-m-octopamine was methylated with CF3SO311CH3 to give 1 suitable for animal and clinical studies. (author)