Intramolecular Azide to Alkene Cycloadditions for the Construction of Pyrrolobenzodiazepines and Azetidino-Benzodiazepines

• Main Authors: Karl Hemming, Christopher S. Chambers, Faisal Jamshaid, Paul A. O'Gorman
• Format: Article
• Language: English
• Published: MDPI AG 2014-10-01
• Series: Molecules
• Subjects: cycloaddition; 1,3-dipole; azide; pyrrolobenzodiazepine; azetidinone; antitumour; antibiotic; β-lactam
• Online Access: http://www.mdpi.com/1420-3049/19/10/16737
• ISSN: 1420-3049

The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs), pyrrolo[1,2,5]benzothiadiazepines (PBTDs), and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics.