10.1081/SCC-120030758
The study presents a facile total synthesis of idarubicinone-7-β-D-glucuronide, an anthracycline antibiotic analog, using a series of carboxylic acid derivatives as key intermediates. The researchers employed polyphosphoric acid (PPA) and AlCl3 as catalysts to cyclize dimethoxybenzene with various carboxylic acid derivatives, yielding naphthalenones, which were further transformed into (+)-idarubicinone 3b. Esterification with (S)-(+)-O-acetylmandelic acid and subsequent separation and deprotection steps led to the isolation of (+)-3b and (2)-3b. These compounds were then glycosylated with acetobromo-α-D-glucuronic acid methyl ester, using ZnBr2 as a catalyst, to produce two kinds of idarubicinone-7-β-D-glucuronide (20 and 21). The synthesized compounds were intended to enhance drug efficacy, potentially improving the pharmacological profile of idarubicinone by attaching glucuronic acid moieties. The study also detailed the synthetic method for an AB-ring synthon necessary for the synthesis of the aglycone and provided a comprehensive analysis of the synthesized compounds using various analytical techniques.