Convergent synthesis of (13)N-labelled Peptidic structures using aqueous [(13)N]NH(3)

BACKGROUND: Nitrogen-13 has a 10-min half-life which places time constraints on the complexity of viable synthetic methods for its incorporation into PET imaging agents. In exploring ways to overcome this limitation, we have used the Ugi reaction to develop a rapid one-pot method for radiolabelling peptidic molecules using [(13)N]NH(3) as a synthetic precursor. METHODS: Carrier-added [(13)N]NH(3) (50 μL) was added to a solution of carboxylic acid, aldehyde, and isocyanide in 2,2,2-TFE (200 μL). The mixture was heated in a microwave synthesiser at 120 °C for 10 min. Reactions were analysed by radio-HPLC and radio-LCMS. Isolation of the target (13)N–labelled peptidic Ugi compound was achieved via semi-preparative radio-HPLC as demonstrated for Ugi1. RESULTS: Radio-HPLC analysis of each reaction confirmed the formation of radioactive products co-eluting with their respective reference standards with radiochemical yields of the crude products ranging from 11% to 23%. Two cyclic γ-lactam structures were also achieved via intra-molecular reactions. Additional radioactive by-products observed in the radio-chromatogram were identified as (13)N–labelled di-imines formed from the reaction of [(13)N]NH(3) with two isocyanide molecules. The desired (13)N–labelled Ugi product was isolated using semi-preparative HPLC. CONCLUSION: We have developed a one-pot method that opens up new routes to radiolabel complex, peptidic molecules with (13)N using aqueous [(13)N]NH(3) as a synthetic precursor. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s41181-017-0035-7) contains supplementary material, which is available to authorized users.