Rapid and simple synthesis for the sulphate esters of 6-hydroxy-melatonin and N-acetyl-serotonin

Melatonin is metabolised by hydroxylation at the 6 position and to a variable extent by demethylation. Both metabolites so formed are excreted as sulphate and, to a lesser extent, glucuronide conjugates. To authenticate these metabolites which we had earlier isolated from urine, we wished to have synthetic samples. Since we also required them as standards we needed them as powders. A review of the literature showed that there were only two published methods, of which only one gave rise to 6-sulphatoxy-melatonin (SaMT) as a solid. The other metabolite, N-acetyl-serotonin-sulphate (SNAS), has not been previously made, and we here describe some of its chemical properties. Our method modifies a published method taking into account the results given in a recent paper describing the sulphation of the thyroid hormones, T3 and T4. Hydroxy-melatonin is thus reacted with a complex formed from dimethylformamide and chlorosulphonic acid. The reaction is of interest since it is rapid, easy, and produces pure powdered material in excellent yield.