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

Oxidative cyclization of bis-hydroxynaphthyl ethers allows concise total sy ntheses 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 trip henyl phosphine was found to be a superior reagent for the rapid preparatio n of a small library of palmarumycin analogs. Preliminary biological evalua tion of naphthoquinone spiroketals against MCF-7 and MDA-MB-231 human breas t cancer cells revealed several low-micromolar growth inhibitors. (C) 2000 Elsevier Science Ltd. All rights reserved.