STRUCTURAL INVESTIGATIONS OF MODE OF ACTION OF DRUGS .2. MOLECULAR-STRUCTURE OF ANTHRAMYCIN METHYL-ETHER MONOHYDRATE

The crystal and molecular structure of C17H19N3O4.cntdot.H2O, an antitumor agent, was determined using X-ray diffraction. The space group is orthorhombic, P212121. The cell dimensions, measured on a diffractometer, are a = 7.984 (1), b = 13.495 (3), c = 16.200 (3) .ANG. and Z = 4. The structure was solved by direct methods and refined by anisotropic least squares to an R index of 0.050. The 1,4-diazepine ring has a boat conformation, while the 5-membered pyrrole ring is a flattened envelope. The stereochemistry at C(12) and C(13) is trans. There are 1 intramolecular and 5 intermolecular H bonds. The methoxy O atom is involved in H bonding. A Kendrew-models study indicates that the anthramycin molecule is most probably covalently bound at C(11) to DNA through N(2) of guanine in the wide groove and O(1) of the anthramycin molecule may be involved in H bonding to sugar O atoms.