Synthesis and some properties of sulfate esters and sulfamates of iodothyronines.
In the present study, convenient methods have been developed for the synthesis of sulfate derivatives of iodothyronines. Reaction with chlorosulfonic acid in dimethylformamide gave rise to formation of the sulfate ester with the phenolic hydroxyl group. Reaction with the sulfurtrioxide-trimethylamine complex in alkaline medium afforded the sulfamate with the alpha-amino group of the alanine side chain. The sulfated products were isolated by adsorption onto Sephadex LH-20 in acidic medium, followed by desorption with water. Iodide was not retarded on these columns, whereas elution of native iodothyronines required alkaline ethanol mixtures. The yield of both reactions varied between 70-90%. The sulfates and sulfamates of T4, T3, rT3, and 3,3'-diiodothyronine could be separated by reverse phase HPLC. The sulfamates exhibited high cross-reactivities with antibodies against free iodothyronines, in contrast to the low activities of the sulfates. Products were further characterized by proton nuclear magnetic resonance, TLC, and hydrolysis by acid or sulfatase activity. The availability of large quantities of pure iodothyronine sulfates and sulfamates should facilitate the study of the importance of sulfate conjugation in the metabolism of thyroid hormone.
D055598:Chemical Phenomena; D002621:Chemistry; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D004104:Diiodothyronines; D004126:Dimethylformamide; D004952:Esters; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008744:Methylamines; D013431:Sulfates / Q000138:chemical synthesis; D013451:Sulfonic Acids / Q000138:chemical synthesis*; D013461:Sulfur Oxides; D013974:Thyroxine / Q000031:analogs & derivatives*; D014284:Triiodothyronine / Q000031:analogs & derivatives; D014285:Triiodothyronine, Reverse / Q000031:analogs & derivatives
D004104:Diiodothyronines; D004952:Esters; D008744:Methylamines; D013431:Sulfates; D013451:Sulfonic Acids; D013461:Sulfur Oxides; D014284:Triiodothyronine; C013880:chlorosulfonic acid; D014285:Triiodothyronine, Reverse; C030629:3,3'-diiodothyronine; D004126:Dimethylformamide; C005741:sulfamic acid; C011118:sulfur trioxide; C023336:trimethylamine; D013974:Thyroxine