Regioselective synthesis of novel 3-thiazolidine acetic acid derivatives from glycosido ureides.

A series of 3-thiazolidine acetic acid-2-(per-O-acetylglycosyl)-1'-imino-α-(substituted)-4-oxo ethyl ester derivatives (3a-t) were prepared via the reaction of substituted amino acid-N-[(per-O-acetylglycosylamino)thioxomethyl]-ethyl ester with ethyl bromoacetate. The crystal structure of 3-thiazolidine acetic acid-2-(2',3',4',6'-tetra-O-acetyl-β-D-galactoyranosyl)-1'-imino-α-methyl-4-oxo ethyl ester 3g and ¹H-¹³C HMBC (2D NMR experiments) measurements of 3-thiazolidine acetic acid-2-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-1'-imino-α-(1-methylthio)ethyl-4-oxo ethyl ester 3j revealed the exclusive regioselectivity during the closure of these rings toward the N-2 position of the thiourea moiety. Furthermore, the crystal structure of compound 3g showed that the attack of N-1 was blocked by sugar ring owing to the steric effect. The bioactivity data suggested that compound 2e has mild anticancer activity.