Anthracyclines. Part 2. Investigations relating to the synthesis of 4-demethoxyanthracyclinones

Abstract

Three strategies for the synthesis of suitably substituted tetrahydronaphthacenequinones related to the 4-demethoxyanthracyclinone series have been investigated. The first, involving conventional Friedel–Crafts annelation required 7-substitution processes at a late stage and proved unsuitable for larger scale preparations. The second and third procedures utilised cyclisation on appropriately substituted, performed A,B-bicyclic systems; they employed a benzeneboronic acid–phthalaldehyde condensation and a Diels–Alder reaction, respectively. The latter process used trans-1,2-diacetoxy-1,2-dihydrobenzocyclobutene to give the appropriate diene in situ. A practicable synthesis of (±)-4-demethoxydaunomycinone has been achieved by this route.