Biosynthesis of piperlongumine

The incorporation of l-U-¹⁴C]lysine and l-U-¹⁴C]phenylalanine into piperlongumine has been demonstrated in Piper longum. The subsequent stepwise degradation to methyl-(3,4,5-trimethoxyphenyl)-propanoate and δ-aminovaleric acid revealed that the C₆-C₃ moiety of the alkamide arises from phenylalanine; the heterocyclic ring is biosynthesised from lysine. It has also been shown that dl-2-¹⁴C]tyrosine and 2-¹⁴C]sodium acetate are poor precursors of piperlongumine.