Solid-Phase Synthesis of PBD Dimers

Significance

The pyrrolo[2,1-c][1,4]benzodia­zepines (PDBs), e.g., DC-81, chicamycin, tomaymycin, are a family of DNA-interactive antitumor antibiotics. Recently, O-alkyl-tethered PDB dimers, such as DSB-120 (6a), have been developed to enhance their DNA-sequence selectivity. This communication described the solid-phase synthesis of a series of PDB dimers. The O-alkyl-tethered anthranilic acid derivatives were immobilized onto Wang resin (compounds 1a-c), and then condensed with prolinol derivatives to give 2 and 3. The hydroxymethyl groups were oxidized under the Swern conditions to afford diazepines 4 and 5. The resulting PDB dimers were cleaved from the resin support by acidic treatment to give the desired O-alkyl-tethered PDB dimers 6 and 7.