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]-9,10-dihydro-6(2 H )-naphthacenone ( 19 ) and (±)-9-carbomethoxy-4,5,12-trimethoxy-11-[(trimethylacetyl)oxy]-9,10-dihydro-6(2 H )-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.