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Structures of Five Components of the Actinomycin Z Complex from Streptomyces fradiae, Two of Which Contain 4-Chlorothreonine

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journal contribution
posted on 12.02.2000, 00:00 by Helmut Lackner, Isabel Bahner, Nobuharu Shigematsu, Lewis K. Pannell, Anthony B. Mauger
Structure elucidation of five components of the actinomycin Z complex (Z1−Z5) isolated from Streptomyces fradiae is described. The components were separated by Si gel column chromatography and TLC/PLC and analyzed by ESIMS, FABMS, LC−MS of derivatized hydrolysates, and 2D NMR techniques. This permitted determination of the complete structures of actinomycins Z1−Z5. In Z3 and Z5, site 1 of the β-depsipeptide is occupied by the rare 4-chloro-l-threonine, an amino acid not previously found in an actinomycin. The structural variants of the actinomycin Z complex have the molecular architecture typical of other actinomycins but possess greater structural diversity resulting from the presence of several highly unusual amino acids. Actinomycins Z3 and Z5, but not Z1, were more potent than actinomycin D in cytotoxicity assays against three tumor cell lines.