Facile Synthesis of 15N-Labeled Amino Acids Using 15N-Ammonium Salt

Abstract

¹⁵N-Labeled amino acids are utilized across a wide range of research fields in biology and chemistry. However, ¹⁵N-labeled materials are typically not readily available, hindering broader applications despite their versatility. In this study, we developed a facile synthetic method for ¹⁵N-labeled amino acid hydrochlorides, using a cost-effective and easy-to-handle ¹⁵N-ammonium salt as the ¹⁵N source. This method employs ¹⁵N-labeled phthalimide as a key synthetic intermediate, which is subsequently coupled with hydroxy acid derivatives under Mitsunobu conditions to afford the corresponding amino acids, providing efficient access to various ¹⁵N-labeled amino acids.