Intramolecular azide to alkene cycloadditions for the construction of pyrrolobenzodiazepines and azetidino-benzodiazepines

Molecules. 2014 Oct 17;19(10):16737-56. doi: 10.3390/molecules191016737.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry*
  • Antibiotics, Antineoplastic / chemical synthesis*
  • Azides / chemistry*
  • Benzodiazepines / chemical synthesis*
  • Cycloaddition Reaction
  • Molecular Structure
  • Pyrroles / chemical synthesis*

Substances

  • Alkenes
  • Antibiotics, Antineoplastic
  • Azides
  • Pyrroles
  • pyrrolo(2,1-c)(1,4)benzodiazepine
  • Benzodiazepines