A concise synthesis of the naphthalene portion of purpuromycin

A concise synthesis of naphthalene compounds for incorporation into a synthetic sequence for the rubromycin family of natural products is presented. These highly substituted naphthalenes are generated in seven and nine steps, respectively, from 2,4,5-trimethoxybenzaldehyde. Three ring-forming methods were explored and the controlled oxygenation of different positions was investigated to yield differentially substituted/protected systems. Key steps to the final products include a Stobbe condensation to form the ring system and a novel series of regioselective oxidations to introduce the required oxygen functionality. These naphthalene products incorporate orthogonal protecting groups and are suitable for combination with a variety of coupling partners.