Structure of Daunomycin; X-ray Analysis of N-Br-Acetyl-Daunomycin Solvate

Abstract

THE antibiotic daunomycin was discovered and studied by Di Marco and co-workers^1–5 who found it to have cytotoxic and antimitotic activity. Extensive chemical work by Arca-mone and co-workers^6–9 has established the total absolute configuration as in Fig. 1, which gives the formula of the N-Br-acetyl derivative. Daunomycin interferes with nucleic acid metabolism in both mammalian¹⁰ and bacterial¹¹ cells, and the formation of a complex between daunomycin and nucleic acids has been studied^12–16. The nature of the chemical binding between antibiotics which affect ribonucleic acid synthesis and DNA has been discussed¹⁶ and it has been suggested that the amino as well as either quinone^17,18 or hydroxyl groups of the chromophore are responsible for hydrogen bonding to the DNA helix. An understanding of this effect is important as the binding of daunomycin to DNA is most likely responsible for the biological activity of this antibiotic. To determine the detailed stereochemical features of daunomycin, the relative orientation of the sugar ring to the aglycone moiety and the nature of the hydrogen bonding in the solid state, we began X-ray crystallographic studies.