Synthesis and chemistry of quinone methide models for the anthracycline antitumor antibiotics

In an effort to further understand the chemistry of anthracycline-type quinone methides, two tetracyclic o-quinone methides, 4,5,12-trimethoxy-11-[(trimethylacetyl)oxy]-3-9,10-dihydro-6(2H)-naphthacenone (19) and (+/-)-9-carbomethoxy-4,5,12-trimethoxy-11-[(trimethylacetyl)oxy]-9,10-di-hydro-6(2H)-naphthacenone (20), were synthesized, and their reaction with several nucleophiles was investigated. Carbon-and sulfur-based nucleophiles afforded stable adducts while oxygen-and nitrogen-based nucleophiles afforded unstable adducts due to the reversibility of the addition. Adducts of 19 with ethanol and O-silylated adenosine (27) were acetylated to afford stable phenol acetates 21 and 29, respectively.