Chemoresistance has emerged as a critical barrier in the treatment of lung cancer. The recently discovered DNA repair enzyme, tyrosyl-DNA phosphodiesterase 2, can repair topoisomerase 2-mediated DNA damage, thereby contributing to cancer cell resistance. This study reported the identification of the natural product myrtucommulone D as a selective tyrosyl-DNA phosphodiesterase 2 inhibitor and presented its first enantioselective total synthesis. The enantiomeric excess (ee) of (+)- and (-)-myrtucommulone D was determined to be 95.3 and 95.1%, respectively. Biological experiments indicated that ...
