DL‐homoserinehydroxamic Acid, DL‐homo‐cystinedihydroxamic Acid, and Derivatives by Hydroxylaminolysis of γ‐Hydroxy‐ and γ‐Thio‐Lactones

Abstract

The reaction of a-amino-, a-carbamoylamino-, a-benzamido-, and a -benzyloxycarbonylamino-y-buryrolactone with hydroxylamine led to the formation of DL-homoserinehydroxamic acid and a -N-acyl derivatives. a-N-Benzoyl-DL-homoserine-N-methyl-hydroxamic acid and 0-benzylhydroxamic acid ester were prepared by reacting a-benz amido-y -butyrolactone with N-methylhydroxylamine and with O-benzylhydroxylamine, respectively. Hydroxylaminolysis of DL-homocysteinethiolactone and of N-acyl-DL-homocysteinethiolacrones gave homocystinedihydroxamic acid and N,N'-disubstiruted derivatives. Relative reactivities of 0-and S-lacrones were compared. a -Amino hydroxamic acids have been prepared by the procedure known for other hydroxamic acids, from a -arnino acid esters and hydroxylamine in alcoholic solution [1]. An additional general method of obtaining a-amino hydroxamic acids is to react a-amino-acid N-carboxyanhydrides with hydroxylamine hydrochloride [2]. The preparation of a-amino l3-functional hydroxamic acids was developed during work on syntheses of the antibiotic cycloserine (oxamycin), an a-amino-l3-hydroxy cyclic hydroxamic acid ester (D-4-amino-3-isoxazolidinone) [3].We considered a-amino--y-butyrolactone (homoserine lactone) and a-amino--y-thiobutyrolactone (homocyste ine lactone) appropriate for the synthesis of o-arnino-v-hydr-o xy-and a-amino--y-thio-butyrhydroxamic acids. Hydroxylaminolysis of a-amino-and a-acylamino-rt-butyrolactoneo-Amino-, a-carbamoylamino-, c-benz amido-, and a-benzyloxycarbonylarnino-v-butyr-o lac tone were brought to reaction with ethanolic hydroxylamine. The reaction was carried out at room temperature, the mixtures being kept for 24 hr. The hydroxamic acids precipitated from the reaction mixture, or were obtained after removal of the solvent and recrystallisation from ethanol-water or propan-2-ol (see Table I) .