Sulfoconjugation of dopamine. A critical examination of the reaction between dopamine and concentrated sulfuric acid

Dopamine, a physiologically important biogenic amine, is readily sulfoconjugated in vivo to give the 3- and 4-O-sulfates of pharmacologic importance. A major synthetic source of these esters has involved reaction of dopamine with sulfuric acid; however, the homogeneity of the products of this apparently straightforward reaction has been questioned. For this reason, in the present study this reaction was studied in considerable detail and our results establish that the concern about the authenticity and purity of dopamine-O-sulfates used for pharmacological studies is justified. In addition to the esters, difficultly separable dopamine-2, -5, and -6-sulfonic acids, plus several unidentified products, were obtained. A detailed account of the isolation and physicochemical characteristics of the identified products is presented. The dopamine-O-sulfates, whose structures have recently been established unequivocally by single crystal X-ray diffractometric analysis in this laboratory, were further characterized by means of mass (electron impact, field desorption, and fast atom bombardment) and 1H and 13C nuclear magnetic resonance spectroscopy. In addition, redox potentials for the isolated reaction products, as well as high performance liquid chromatography, thin-layer chromatography, and color reactions of the dopamine-O-sulfates, are reported. Thermolysis of the 3- and 4-O-sulfates yielded similar mixtures of products.