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A synthesis of 4·amino·3·isoxazolidinone (I) (Cycloserine) pivoting on 1·t rityl-2-carbomethoxyethyleneimine (IV) is described. This key intermediate was prepared from N-tritylserine m ethyl ester via theO-mesylderivative in 80 % overall y ield. The hydroxamic acid VII corresponding to this ester on treatment with hydrogen chloride yielded 66 % of the hydrochloride of a:-amino -~-ch lo ropropiohydl'oxamic acid (X) together with a small amount of its position isomer XI. The former isomer was converted to 4-amino·3--isoxazolidinone (I) by treatm ent with a lkali or with strongly basic anion exchangers .4-Benzylamino-3-isoxazolidinone (Va) and 4-benzhydrylamino-3-isoxazolidinone (Vb) we re synthesised as models.The antibiotic cycloserine (Oxamycin, Seromycin), isolated in 1955 from a strain of St1'eptomyces\ possesses a broad antibacterial spectrum2, low toxicity and has been found to give encouraging results in the chemotherapy of tuberculosis, particularly with streptomycin and isonicotinyl hydrazide resistant strains 4 • It has also been found to be a powerful synergist of other antibiotics 5 and is hence thought to be a drug of high promise.The structure of the antibiotic as D-4-amino-3-isoxazolidinone (1) and its first synthesis have been disclosed in preliminary form 6 -B • In view of its relatively simple structure and clinical promise cycloserine thus is the second antibiotic -following chloramphenicol -whose production by synth esis rather than by fermentation appears as a practical possibility. Synthetic work in this field, attractive from the theoretical point of view on account of the somewhat unusual structure of cycloserine, thus also possesses considerable practical inter est.Little attention had hitherto b een devoted to the isoxazolidinone system. An analysis of the possible synthetic approaches to an aminoisoxazolidinone shows that the key step of its synthesis, i. e. the ring closure, can in principle be realised in two alternative ways. The first is the amidic ring closure of an ester of an lX-amino-~-aminooxypropionic acid (a), the second is the cyclisation of an cx-amino-~-halogenopropiohydroxamic acid or its derivatives (b).CHz-CH-COOCH a ~

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