The synthesis of benzoquinone natural product 2 and three analogues is described. The synthesized compounds were tested for their ability to protect Friedreich's ataxia (FRDA) lymphocytes from induced oxidative stress. One of the analogues (3) conferred cytoprotection in a dose-dependent manner in FRDA lymphocytes at micromolar concentrations. The biological assays suggest that the modification of the 2-hydroxy and N-(3-carboxypropyl) groups in the natural product can improve its antioxidant activity and significantly enhance its ability to protect mitochondrial function under conditions of oxidative stress.