Regio- and Diastereoselective Arylation of rosin acids: A practical strategy for bioactive compounds discovery

A mild, sustainable, and cost-effective arylation of rosin-acids is reported. This new approach, based on a regio- and diastereoselective Friedel-crafts alkylation, enabled the synthesis of fourteen new resin acid derivatives. Selected compounds were screened for cytotoxic activity against three human tumor cell lines. Remarkably, quinone 14 exhibited significant activity: Against HL-60 cells (IC₅₀ = 5.94 μ M) cell, and phenol 11f displayed selective cytotoxic activity against HT-29 cells (IC₅₀ = 8.90 μ M) cells. Flow cytometry confirmed apoptosis as the primary mechanism of cell death, reaching 78% in HL-60 ( 14 ) and 72.6% in HT-29 ( 11 g ), with minimal necrosis. Cell-cycle analysis showed S-phase arrest in HL-60 ( 14 ) and G 0 /G 1 arrest in HT-29 ( 11f / 11 g ). Consistently, ΔΨm assays showed near-complete collapse in HL-60 ( 14 ) and significant depolarization in HT-29 ( 11 g ). In addition, the anti-inflammatory activity of some synthesized compounds was assessed in LPS-stimulated RAW 264.7 macrophages. All tested compounds achieved 70–100% NO inhibition at subcytotoxic concentrations. Derivatives 13 and 14 showed the highest activity (IC 50 NO = 0.85 μM and 5.43 μM, respectively). Overall, this green arylation approach enables rapid access to 7-aryl methyl ester dehydroabietic acid libraries with significant cytotoxic and anti-inflammatory activities • Mild, sustainable, and cost-effective arylation of rosin-acids • Synthesis of fourteen new resin acid derivatives • Quinone 14 exhibited significant cytotoxic activity: against HL-60 (IC₅₀ = 5.94 μM) cell • Derivatives 13 and 14 showed the highest Anti-inflammatory activity (IC 50 NO = 0.85 μM and 5.43 μM, respectively)