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

Article abstract of DOI:10.1002/jlcr.2580360703

(-)-[¹¹C]Phenylephrine and positron emission tomography could potentially be used to assess neuronal monoamine oxidase activity in the heart. Previous data for (-)-[¹¹C]phenylephrine indicated 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, 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-octopamin, (-)-α,α-Dideutero-m-octopamine was methylated with CF₃SO₃¹¹CH₃ to give suitable for animal and clinical studies.