The Synthesis of Functionalized Pyrrolo-[2,1-c][1,4]-Benzodiazepines

Two concise and high yielding routes to the antitumour antibiotic pyrrolo-[2,1-c][1,4]-benzodiazepine ring system are described. Thus, condensation of prolinol with 2-azidobenzoylchloride gives the tertiary amide (3). Oxidation to the aldehyde (4) followed by generation of the phosphoroimine by Staudinger reaction results in ring closure via an aza-Wittig reaction to yield the desired ring system. Alternatively, coupling of prolinol with the appropriate isatoic anhydride yields the corresponding amino alcohol. Oxidation with Dess-Martin periodinane yields the PBDs in moderate to good yield.

pyrrolo-[2,1-c][1,4]-benzodiazepine - Dess-Martin periodinane - palladium coupling - DNA binding