Conformational energetics of sugar thioureas and synthesis of glycosyl thioureido sugars

Article abstract of DOI:10.1016/0040-4020(96)00673-4

The rate and outcome of the reaction of 6-deoxy-6-isothiocyanatoaldopyranoside derivatives with ammonia depend strongly on the nature of the hydroxyl protecting groups and solvent. In pyridine as solvent, the expected thioureas are obtained as the sole reaction products. A marked preference for the E configuration at the sugarNH-C(=S) bond is observed for silylated as compared to acetylated derivatives. Rotational barrier calculations, temperature-induced NH shifts, and other NMR data indicate a strict relationship between the E rotamer population and the existence of an intramolecular NH···O-5 hydrogen bond that fits a pseudo γ-turn. Competition between inter- and intra-molecular hydrogen bonding rather than steric factors probably explain these results. Acetal and trimethylsilyl ether derivatives have been further used in the preparation of fully unprotected derivatives. The procedure has been extended to the first synthesis of (1 → 6)-linked glycosyl phosphosugar analogues incorporating thiourea bridges as phosphate surrogates.