10.1021/ja00344a031
The research focuses on the development of an improved synthetic route to 4-demethoxydaunomycinone (24), a significant intermediate in the synthesis of the antineoplastic drug 4-demethoxydaunomycin. The study explores the functionalization of the A-ring of tetracyclic precursors, particularly the introduction of the cis-7,9-diol functionality and the resolution of racemic 4-demethoxy-7-deoxydaunomycinone (16) into its enantiomers using Enders' hydrazine reagent. Key chemicals involved in the research include 4-demethoxy-7,9-dideoxydaunomycinone (4), its dimethyl ether (5), various reagents such as perchloric acid, acetic anhydride, m-chloroperbenzoic acid, and sodium hydroxide for the functionalization steps, and Enders' hydrazine reagent for the resolution process. The research also involves the synthesis and characterization of several intermediate compounds, such as enol acetate 7, epoxy acetate 12, hydroxy ketones 16 and 19, and the 7-bromo derivatives 21 and 22, which are crucial for achieving the desired functionalization and resolution. The study provides detailed procedures and conditions for the synthesis of these compounds, contributing to the development of a practical and efficient route for the preparation of 4-demethoxydaunomycinone in multigram quantities.
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.