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

✍ Scribed by R. B. Del Rosario; D. M. Wieland

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 288 KB
• Volume: 36
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580360703

✦ Synopsis

Abstract

(−)‐[^11^C]Phenylephrine and positron emission tomography could potentially be used to assess neuronal monoamine oxidase activity in the heart. Previous data for (−)‐(^11^C]phenylephrine indicate that, although its retention and neuronal selectivity parallel that of the neuronal mapping agent (−)‐[^11^C]hydroxyephedrine, its neuronal storage and clearance properties are quite different. In order to study the in vivo kinetics of (−)‐[^11^C]phenylephrine in greater detail, the dideutero analog [^11^C]‐(−)‐α,α‐dideutero‐phenylephrine, 1, was synthesized by [^11^C]methylation of the precursor (−)‐α,α‐dideutero‐m‐octopamine. The key step in the procedure was BD~3~ 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 CF~3~SO~3~^11^CH~3~ to give 1 suitable for animal and clinical studies.