In this work twelve benzo[k,l]xanthene lignans were synthesized by biomimetic, Mn-mediated oxidative coupling of caffeic esters and amides. These compounds, bearing different flexible pendants at position C1/C2 of the aromatic core, interact with DNA in a dual mode, as confirmed by DF-STD NMR analysis and molecular docking: the planar core acts as a base pair intercalant, whereas the flexible pendants act as minor groove binders. Their antiproliferative activity was evaluated on a panel of six tumor cell lines: HT-29, Caco-2, HCT-116 (human colon carcinoma), H226, A549 (human lung carcinoma), and SH-SY5Y (human neuroblastoma). All compounds under study, except 29, resulted in activity against one or more cell lines, and the markedly lipophilic esters 13 and 28 showed the highest activity. Compound 13 was more active than the anticancer drug 5-fluorouracil (5-FU) towards HCT-116 (colon, GI50 = 3.16 μM) and H226 (lung, GI50 = 4.33 μM) cell lines.

Seven resveratrol‐related monomeric stilbenoids were submitted to biomimetic oxidative coupling in the presence of laccase from Trametes versicolor (TvL), and gave racemic dihydrobenzofuran dehydrodimers (±)‐15 to (±)‐21. These products, after spectral characterization, were submitted to an antiproliferative activity bioassay against SW480 human colon cancer cells. Five racemates were found to be active, and were resolved by chiral HPLC. The pure enantiomers were subjected to circular dichroism measurements to establish their absolute configurations at C‐7 and C‐8. These enantiomerically pure compounds were submitted to the antiproliferative activity assay towards SW480 cells, and were all shown to be active with IC50 values in the approximate range 20–90 μM. In some cases, a significant difference between the activity of the 7R,8R and 7S,8S enantiomers was observed, but a defined configuration of the stereogenic centers does not appear to be a structural requirement for the activity. The comparison between the most active compounds and the inactive ones strongly suggests that the presence of a methoxy group in the position ortho to the C‐4 hydroxy group is highly detrimental to the activity.

The unprecedented green, stereoselective, and enzymatic synthesis of biologically remarkable hydantoin derivatives through an intramolecular anti-aza-Michael addition.