Rapid one-pot radiosynthesis of [carbonyl-C]formamides from primary amines and [C]CO.

BACKGROUND

Formamides are common motifs of biologically-active compounds (e.g. formylated peptides) and are frequently employed as intermediates to yield a number of other functional groups. A rapid, simple and reliable route to [carbonyl-C]formamides would enable access to this important class of compounds as in vivo PET imaging agents.

RESULTS

A novel radiolabelling strategy for the synthesis of carbon-11 radiolabelled formamides ([C]formamides) is presented. The reaction proceeded with the conversion of a primary amine to the corresponding [C]isocyanate using cyclotron-produced [C]CO, a phosphazene base (2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine, BEMP) and phosphoryl chloride (POCl). The [C]isocyanate was subsequently reduced to [C]formamide using sodium borohydride (NaBH). [C]Benzyl formamide was obtained with a radiochemical yield (RCY) of 80% in 15 min from end of cyclotron target bombardment and with an activity yield of 12%. This novel method was applied to the radiolabeling of aromatic and aliphatic formamides and the chemotactic amino acid [C]formyl methionine (RCY = 48%).

CONCLUSIONS

This study demonstrates the feasibility of C-formylation of primary amines with the primary synthon [C]CO. The reactivity is proportional to the nucleophilicity of the precursor amine. This novel method can be used for the production of biomolecules containing a radiolabelled formyl group.