“Reverse chromophore” of actinomycin d. Synthesis of 2-substituted 7-amino-8H-8-oxo-oxazolo[4,5-b] phenoxazine ring system

The synthesis and physico-chemical properties of a new 7-amino-8H-8-oxo-oxazolo[4,5-b]-phenoxazine ring system (8a and 8b) are reported. These tetracyclic heteroaromatic rings posses an extra oxazolo ring fused to the phenoxazinone chromophore observed in actinomycin D (1b). These tetracyclic compounds (8a-8b) possess a structure in which the orientation of the A and B rings in 1b are “reversed”. Since DNA binding and the resulting specificity of the antitumor antibiotic 1b is believed to depend on the spatial orientation of P(α) and P(β) relative to the functions on the B ring of 1b , these new compounds represent a novel approach for investigating AMD-DNA interactions.