The reduction of alpha-ketocarboxylic acids and alpha-dicarbonyl compounds with titanium(III) chloride.

Thirteen model alpha-ketocarboxylic acids and alpha-dicarbonyl compounds have been observed to be reduced by titanium(III) chloride. The products of these reactions were shown by melting (boiling) points, mixed melting points, derivatives, refractive indices, infrared, and NMR comparisons with authentic compounds or literature information to be the corresponding alpha-hydroxycarboxylic acids or alpha-hydroxyketones.

The reduction of aliphatic and aromatic N-oxides to the corresponding amines with titanium(III) chloride.

Amine N-oxides have been observed to be reduced by titanium(III) chloride. To study this reaction, 24 model amine N-oxides were reacted with titanium(III) chloride. The products of these reactions were shown by melting (boiling) points, mixed melting points, derivatives, refractive indices, infrared, and NMR comparisons with authentic compounds to be the corresponding amines. The reductions were found to require 2 moles of titanium(III) per mole of amine N-oxide.

The reduction of hydroxamic acids with titanium(III) chloride: a tool for the characterization of siderophores.

Hydroxamic acid siderophores were observed to be inactivated by exposure to titanium(III) chloride. To study the reaction, a series of eight model hydroxamic acids were prepared and reacted with titanium(III) chloride. The products were shown by ir and NMR comparisons with authentic compounds to be the corresponding amides. The reduction was found to require 2 mol of titanium(III) per mol of hydroxamic acid.

Isolation of the siderophore schizokinen from soil of rice fields.

Schizokinen, a siderophore previously isolated from low-iron cultures of Bacillus megaterium and Anabaena sp., was isolated from the soil of rice fields after the annual flooding period.

Thujaplicins from Thuja plicata as iron transport agents for Salmonella typhimurium.

Strains of Salmonella typhimurium which are unable to synthesize their normal iron transport agent, enterobactin, and which must be supported with an exogenous chelator (siderophore) on certain media, were used to examine various types of wood for the presence of chelators. Western red cedar wood, Thuja plicata, was observed to contain large amounts of three substances that in low concentration would serve as chelators for S. typhimurium. The chelators from T. plicata were characterized and found to be alpha-, beta-, and gamma-thujaplicin. Other planar cyclic alpha-hydroxyketones were examined, and several were found to function as chelators for S. typhimurium.

The development of new iron-chelating drugs.

2,3-Dihydroxybenzoic acid has been identified as a potentially useful iron-chelating drug. Accordingly, we have evaluated a series of derivatives of hydroxylated benzoic acids for their ability to induce iron excretion in the iron-overloaded rat. In addition, we have examined a number of hydroxamic acids and some other naturally occurring iron-chelating agents. Of the 26 benzoic acid derivatives studied, none appeared to be more effective than 2,3-dihydroxybenzoic acid, for reasons which are discussed. Rhodotorulic acid, a hydroxamic acid produced by and isolated from cultures of Rhodotorula pilimanae, was the most effective of all the compounds studied in inducing iron excretion. When administered parenterally, rholotorulic acid induced iron excretion via both the urinary and the fecal routes and was more than twice as potent (on a weight basis) as desferrioxamine. Two ferrous chelators, alpha, alpha-dipyridyl ad 1,10-phenanthroline, induced a moderate amount of iron excretion, suggesting that a pool of ferrous iron may be available for chelation.