Structural analogues of anti-cancer natural product, dysideanone, were synthesized starting from Wieland-Miescher ketone derivative. In vitro studies have been conducted to evaluate the anti-cancer potential of these unnatural meroterpenoids against colon cancer. Synthesized carbotetracycles were found to be more active as compared to their acyclic carbinol-derivatives. Unnatural carbotetracycles 4b-e, 4h, 4i and 12 were found to be highly effective against the human colon adenocarcinoma cells with IC<sub>50</sub> concentrations of 7.5-20 μM. In this series, the carbotetracyclic catechol 4e (IC<sub>50</sub> = 7.5 μM) and quinone 12 (IC<sub>50</sub> = 8 μM) were found to be the most potent compounds having the IC<sub>50</sub> of less than 10 μM with no cytotoxic effect on the normal cells. Downregulation of Cox-2 and survivin and cell cycle arrest eventually leading to apoptosis were found to be the underlying mechanism of the anti-cancer effect of these unnatural meroterpenoids.