A Novel Approach To Phenanthridinone And Its Derivatives Through Fe (Ⅲ)-mediated Oxidative C-C Coupling Reaction

Benzo[c]phenanthridines are naturally occurring alkaloids with various biologicalactivities. In particular, benzo[c]phenanthridinium salts such as nitidine, fagaronine,sanguinarine, and chelerythrine display remarkable antitumor properties. These compounds wereisolated from Rutaceous and Papaveraceous plants. Although Nitidine and fagaronine wereexpected to be useful antitumor drugs because of their strong activity against several tumor cells,a preclinical NCI investigation revealed that Nitidine displayed a narrow antitumor spectrum, anacute toxicity and instability in1976, Therefore, attention is still focused on the development ofconvenient and effective methods for synthesizing their analogues, expecting to find morepromising compounds.Among so many papered methods, two main strategies have been commonly employed:(i)reductive amination of2-aryltetralones and subsequent heterocyclizaiton, and (ii) theintramolecular biaryl coupling of benzylnaphthylamines bearing the adequate functional group inthe benzyl ring. In the latter case, radical, photochemical and benzyynemediated synthesis of thebenzophenanthridine skeleton have been reported.Based on our previous investigation, we proposed a short and efficient access tophenanthridinone and its derivatives through Fe (III)-mediated oxidative free radical cyclizationreactions starting from N-phenyl benzamides and N-methyl phenylbenzamides. And then a studyof the electronic and steric requirements of the substrates is carried out since, in some case,dimerization processes prevail over intramolecular cyclization.The structures of the compounds were characterized by LRMS,1H&13C NMR spectrasand X-ray analysis. Mechanisms were studied for the reaction process, and one possiblemechanism was proposed.