Scheme 1.

Synthesis of doxazolidine and doxoform by reaction of doxorubicin with formaldehyde and virtual crosslinking of DNA at a 5′-NGC-3′ site by doxazolidine. N and N’ represent unspecified, complementary bases. The structure of the virtual crosslink is also shown with a three-dimensional model, with N equal to C and N’ equal to G, created using coordinates from Rutgers Protein Database (PDB code 1D33) for the Wang crystal structure ¹⁵ of the daunorubicin virtual crosslink of 5′-CGCGCG-3′ using Chem 3D and Pymol.