Endogenous Alkaloids in Man, Part 33. Dimethyl (2S,4S)-and (2R,4S)-5,5-Dimethyl-1,3-thiazolidine-2,4-dicarboxylates, Two Diastereomeric Glyoxylate-Derived Heterocycles

Both title compounds were obtained in stereochemically pure form by refluxing 5,5-dimethyl-1,3-thiazolidine-2,4-dicarboxylic acid (3) with methanolic HCl. followed by a separation of the two diastereomers 4a and 4b on silica gel. The X-ray structure analyses of these stereoisomers confirm the relative configuration to be cis for 4a and trans for 4b with respect to the two carboxymethyl sudstituents at C(2) and C(4). For both molecules, an envelope-type conformation of the thiazolidine ring was found with C(5)-S(1)-C(2)-N(3) being located in a plane showing a small ring torsion angle of -11.2 degrees and -3.1 degrees for the cis- and the trans-epimer. respectively. The trans-configured compound 4b adopts a nearly ideal envelope conformation with C(4) being the flap atom, while the cis-isomer 4a, apparently because of steric interactions of the C(2) and C(4) substituents. shows a twisted envelope conformation.