Synthesis and biological evaluation of deoxypreussomerin A and palmarumycin CP1 and related naphthoquinone spiroketals

Oxidative cyclization of bis-hydroxynaphthyl ethers allows concise total syntheses of palmarumycin CP1 and deoxypreussomerin A in 8-9 steps and 15–35% overall yield from 5-hydroxy-8-methoxy-1-tetralone (8). Polymer-bound triphenyl phosphine was found to be a superior reagent for the rapid preparation of a small library of palmarumycin analogs. Preliminary biological evaluation of naphthoquinone spiroketals against MCF-7 and MDA-MB-231 human breast cancer cells revealed several low-micromolar growth inhibitors.