Preparation of d-, dl-, and l-homoserine lactone from methionine

A practical procedure is described for the replacement of the methylmercapto group of the readily available d- and l-methionine with an hydroxyl group, thus forming the d and l forms of homoserine, in a high degree of purity. Yields were in excess of 75%. Methionine was allowed to react with a stoichiometric amount of bromoacetic acid in a 20% acetic acid solution of water and isopropanol, 1:1, at reflux temperature. The resultant homoserine hydrobromide was cyclized by treatment with 4 M HCl in dioxane. The p-toluenesulfonyl derivatives were made of natural l-homoserine lactone and that prepared from l-methionine. There were no significant differences in physical properties or composition. The homoserine lactones and their tosyl derivatives were reacted with hydroxyl amine to form the hydroxamic acids. These compounds are stable at neutral or alkaline pH, as in the extracellular fluids of animals, but slowly release hydroxyl amine at acid pH, as in the nucleus or mitochondria. This is of interest since hydroxyl amine reacts with purines and pyrimidines and is a mutagenic substance.