A model compound of actinomycin. Conformation of dimethyl actinocynilbis(sarcosyl-L-valinate)

The actinomycin analog I (Sar = MeNCH2CO) was prepd. by acylating H-Sar-Val-OMe with 3-benzyloxy-4-methyl-2-nitrobenzoyl chloride, hydrogenating the resulting nitrobenzoyl peptide II over Pd/C, and cyclocondensing the resulting aminobenzoyl peptide III by oxidn. with K3Fe(CN)6. The conformation of I was analyzed by NMR, CD, and model-building data. The steric hindrance due to the methylation of the phenoxazinone bridging peptides does not allow coplanarity between the peptides and the phenoxazine group. This coplanarity exists in other actinomycin models. I does not intercalate into DNA.