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A stereoselective three-step synthesis of the title thiazolidine-4-carboxylic acids (III), potential lead compounds for the development of antihypertensive drugs with angiotensin converting enzyme inhibitory activity, starting from natural L-cysteine (I) is given.

Condensation products of title hydrazone with aliphatic and aromatic aldehydes as well as aldoses are synthesized.

The reaction of 5-hydroxy-3,3,5-trimethylisoxazolidine with methyl, ethyl, and tert-butyl acrylates, proceeds as Michael addition, and produces previously, unknown 5-hydroxy-3,3,5-trimethylisoxazolidine-2-propionic acid esters. The structures of the obtained products are proved by1H and13C NMR spectroscopy and by their subsequent transformation into 5-hydroxy-3,3,5-trimethylisoxazolidine-2-propionic acid.

Condensation products of thioglycolic acid hydrazide with aldoses (L-arabinose, D-xylose, L-rhamnose, D-galactose, D-glucose, D-mannose) exist in the D2O solution as a tautomeric mixture of α,β-pyranose form and six-membered 1,3,4-thiadiazine form present as two diastereomers.

Condensation products of aroylacetic aldehydes with hydrazides of thioglycolic, 3-mercaptopropionic and 2-mercaptobenzoic acids exist in cyclic 1,3,4-thiadiazine, 1,3,4-thiadiazepine, or 1,3,4-benzothiadiazepine forms arising at the intramolecular addition of the mercapto group to the C=N bond of the initially formed hydrazone tautomer. The appearance of an alternative 5-hydroxy-2-pyrazoline form is favored by introduction of a strong electron-acceptor substituent into the aromatic ring of the 1,3-ketoaldehyde or by going over to benzoylacetone derivatives. In solutions the derivatives of aroylacetic aldehydes and of benzoylacetone show no tendency to tautomeric transition into linear hydrazine or enhydrazine forms.

The products of the condensation of 5-hydroxy-3,3,5-trimethylisoxazolidine (1) with 4-phenylthiosemicarbazide and 2-methyl-4-phenylthiosemicarbazide have predominantly isoxazolidine or 1,2,4-triazolidine structure and do not display ring-ring tautomeric interconversion in solution [1]. Such tautomerism was discovered in studying the structure of 2a and 2b, which are the products of 1 with 4-methyland 2,4-dimethylthiosemicarbazides. Thiones 2a and 2b are formed after brief heating of the starting reagents in methanol at reflux in the presence of catalytic amounts of acetic acid.