Studies on pyrazines. Part 37. Synthesis of 6-propionylpteridine-2,4(1H,3H)-dione and its 1- and/or 3-methyl derivatives from marine natural products

Abstract

The synthesis of 1,3-dimethyl-6-propionylpteridine-2,4(1H,3H)-dione is described, which is completed by the cross-coupling reaction of 6-bromolumazine with a 1-ethoxyprop-1-enyl tin compound in the presence of a palladium catalyst and copper iodide. Similarly, 1,3-demethylated, and 1- and 3-methyl derivatives are prepared from the corresponding bromolumazines which are obtained by cyclization of 6-bromo-3-acetylamino- or -3-methylamino-pyrazinecarbonitrile with methyl isocyanate or methyl chloroformate. In contrast, the synthesis of 6-propynyllumazine relies on the palladium-catalyzed cross-coupling reaction of 6-bromo-3-methylaminopyrazinecarbonitrile with propyne, yielding 6-acetonylpteridine on treatment with aqueous mercury(II) sulfate.