Isolation and biomimetic synthesis of phenylpropionyl phenylethylamines from Chloranthus henryi

In this study, ten phenylpropionyl phenylethylamines, including five previously undescribed ones (1a/b, 2a/b, and 3), five known analogues (4 – 8), and two established phenylpropanoids precursors (9, 10) were isolated from the aerial parts of Chloranthus henryi Hemsl. Their structures, including absolute configurations, were determined by high-resolution mass spectrometry, enantio-separation, electronic circular dichroism calculation, and single crystal diffraction. Compounds 1a and 1b were the first examples of natural hetero-[2 + 2] cycloaddition products between phenylpropionyl phenylethylamine and phenylpropene. The plausible hetero-[2 + 2] biosynthesis pathway was confirmed by a photocatalytic biomimetic synthesis in eight steps, which also led to the production of three other potential natural homo-[2 + 2] adducts (1′a/b, 2′, and 3′). Bioactivity screening indicated that these adducts bear medium inhibitory activity on nitric oxide generation, with IC50 values of 6 – 35 μM in RAW 264.7 macrophages.