Convenient Syntheses of Daunomycinone‐7‐D‐Glucuronides and Doxorubicinone‐7‐D‐Glucuronides

Abstract

The first synthesis of new doxorubicin and daunomycin analogs containing glucuronic acid moieties instead of daunosamine are described. The desired products, daunomycinone‐7‐D‐glucuronide (DM7G, 10) and doxorubicinone‐7‐D‐glucuronide (DX7G, 11) were conveniently prepared through the glycosylation at 7‐hydroxyl group of daunomycinone (4) or 14‐acetoxydoxorubicinone (6) with glucuronic acid derivative 7 by the Koenigs‐Knorr procedure followed by alkaline deacetylation using aqueous LiOH solution and amberlite cation exchange material. The anomeric configuration and conformation of all products were fully characterized by assignment of ¹H NMR chemical shifts and H‐H coupling constants based on reported literatures.

Keywords:

• Anthracycline
• Daunomycinone
• Doxorubicinone
• Glucuronic acid
• Glycosylation

Acknowledgments

This work was supported by a grant of the Korea Health 21 R & D project (01‐PJ‐PG3‐21500‐0031), Ministry of Health and Welfare. We gratefully acknowledge Korea Basic Science Institute (KBSI) for the NMR and mass analyses.