Antibiotic YC 73 of Pseudomonas origin. 3. Synthesis of thioformin analogues.
In the earlier paper of this series1}, it was reported that YG 73 (I) of a Pseudomonas origin was a cupric complex of an acidic substance named thioformin (II), which could be synthesized by treating N-methylhydroxylamine with potassium dithioformate. Soon after the structure determination of II, the fact that such a simple thiohydroxamic acid derivative as II possesses significant antimicrobial activity prompted us to synthesize structural analogues of II. The analogues represented in the general formula III were readily prepared by the following methods. R\ yS )N-Cf (III) ho/ \h Method A : Direct thioformylation of N-substituted hydroxylamines with potassium dithioformate.
Antibiotic Action of N-Methylthioformohydroxamate Metal Complexes
The antibiotic activity of metal complexes of N-methylthioformohydroxamic acid against gram-negative Escherichia coli NIHJ and gram-positive Staphylococcus aureus 209P was investigated. The kinetically labile, square-planar, divalent (Cu, Ni, and Pd) and octahedral, trivalent (Fe, Co, and Cr) complexes displayed activity, whereas the more inert platinum(II) or rhodium(III) complex displayed no activity, or activity only at elevated concentrations. The free ligand did not suppress the growth of the above organisms, and the sulfur atom of the ligand in its metal complexes appears crucial for activity. Uptake studies of radioactively labeled N-methylthioformohydroxamic acid, its nickel(II), platinum(II), iron(III), and rhodium(III) complexes were conducted in the Escherichia coli K-12 RW193 mutant, which is defective in the production of its native iron(III) transport agent, enterobactin. Uptake of 55Fe or 63Ni label from their metal complexes appeared to occur as free inorganic metal ions. The antibiotic activity of the iron(III) and nickel(II) complexes was not due merely to an enhanced accumulation of metal ions by the cell. Metal complexes of [35S]N-methylthioformohydroxamic acid enhanced the accumulation of 35S label compared to that of the free ligand. The antibiotic activity and uptake data are discussed in terms of possible modes of action.
Stoffwechselprodukte von Actinomyceten. 27. Mitteilung. Über die Konstitution von Ferrioxamin B
Ferrioxamine B, the main sideramine type growth factor isolated from cultures of Streptomyces pilosus ETTLINGERet al., is a racemic trihydroxamate-iron(III) complex of the compound IV. The possible configurations for the iron(III) complex are Va–e.