Antibiotics GE23077, Novel Inhibitors of Bacterial RNA Polymerase: II. Structure Elucidation

During the screening program for new antibacterial agents produced by actinomycetes, GE23077 was isolated from fermentation broths of an Actinomadura sp. strain as a complex of factors A1, A2, B1, B2.NMR, MS and GC/MS analysis carried out on the isolated components led to the conclusion that GE23077 is a novel cyclic heptapeptide consisting of common and unusual amino acids. The chemical structures of the complex components were elucidated.Components A and B differ in the structure of the acyl group connected to a 2,3-diaminopropanoic acid moiety. A α-amino-malonic acid residue in the peptidic sequence is the origin of an isomerization process between A1 and A2 as well as B1 and B2. The chirality of the α-amino-malonic acid residue can be inverted easily via keto-enol tautomerism. Factors A2 and B2 should be considered as epimers of A1 and B1 respectively.By degradation studies the absolute configuration of some amino acids were determined. Chiral GC-MS and Micellar Electrokinetic Capillary Chromatography (MEKC) were used to define the absolute stereochemistries of five out of ten chiral centers.