Facile total syntheses of idarubicinone-7-β-D-glucuronide: Convenient preparations of AB-ring synthon using some carboxylic acid derivatives

Regiospecific syntheses of idarubicinone coupled with D-glucuronic acid are described. Cyclization of dimethoxybenzene with carboxylic acid derivatives in polyphosphoric acid (PPA) in one step afforded the naphthalenones 7, which were transformed to the (±)-idarubicinone 3b by general methods. Esterification of (±)-3b with (S)-(+)-O-acetylmandelic acid with subsequent separation and deprotection gave (+)-3b and (-)-3b. Reaction of separated two stereoisomers with acetobromo-α-D-glucuronic acid methyl ester respective followed by hydrolysis using lithium hydroxide and amberite cation exchange resin furnished two kinds of idarubicinone-7-β -D-glucuronide (20 and 21) that are coupled at C-7 position of idarubicinone.