The first total synthesis of (-)-xestosaprol N and O is described. This synthetic work features a convergent strategy: (1) a Pd-catalyzed arylation followed by cyclization to build a naphthalene fragment (ring C, D); (2) utilization of (-)-quinic acid to construct the chiral hydroxyl group at C-2; (3) a substrate controlled intramolecular Heck reaction to construct a quaternary carbon center (ring B); (4) introduction of a hypotaurine moiety at a late stage to furnish the E ring.