Synthesis of ABC Analogues of the Antitumour Antibiotic Streptonigrin

ABC analogues of the antitumour antibiotic streptonigrin, that contain the key metal chelation site and redox-active quinone unit that are essential for biological activity, were prepared via palladium catalysed cross-coupling of 2-iodo-8-nitroquinoline or 2-iodo-6-methoxy-5-nitroquinoline with 2-trimethylstannio-6-methylpyridine. Mild oxidation of the pyridyl methyl group introduced the acid functional group on ring C and Fremyʹs salt oxidation afforded the quinone unit which was elaborated to give the 5-amino-6-methoxy substitution pattern present in streptonigrin.