Facile Total Syntheses of Idarubicinone‐7‐β‐D‐glucuronide: Convenient Preparations of AB‐Ring Synthon Using Some Carboxylic Acid Derivatives

Abstract

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.

Keywords:

• Anthracycline
• Idarubicin analogs
• Glucuronic acid
• Glycosylation

Acknowledgments

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01‐PJ1‐PG3‐21500‐0031). Also we are grateful to KBSI (Korean Basic Science Institute) for NMR and Mass analysis.