Electrosynthesis of N-15-labeled amino acids from N-15-nitrite and ketonic acids

N-15 isotope-labeled amino acids (N-15-amino acids) are crucial in the fields of biology, medicine, and chemistry. N-15-amino acids are conventionally synthesized through microbial fermentation and chemical reductive amination of ketonic acids methodologies, which usually require complicated procedures, high temperatures, or toxic cyanide usage, causing energy and environmental concerns. Here, we report a sustainable pathway to synthesize N-15-amino acids from readily available N-15-nitrite ((NO2)-N-15) and biomass-derived ketonic acids under ambient conditions driven by renewable electricity. A mechanistic study demonstrates a N-15-nitrite ->(NH2OH)-N-15 -> N-15-pyruvate oxime -> N-15-alanine reaction pathway for N-15-alanine synthesis. Moreover, this electro-chemical strategy can synthesize six N-15-amino acids with 68%-95% yields. Furthermore, a N-15-labeled drug of N-15-tiopronin, the most commonly used hepatitis treatment drug, is fabricated using N-15-glycine as the building block. Impressively, N-15 sources can be recycled by the electrooxidation of (NH4+)-N-15 to (NO2)-N-15 with a method economy. This work opens a venue for the green synthesis of N-15-labeled compounds or drugs.