Progress in the synthesis of OPC-15161: Easy access to dioxygenated pyrazine N-oxide structure

An improved synthetic route to OPC-15161 (1), a novel inhibitor of superoxi de anion generation, is described. Choice of the protecting group is the ke y to the second-generation synthesis. Usefulness of the 2-cyanoethyl (CE)-p rotecting group in our process research is emphasized in comparison with th at of other protecting groups. This process can be carried out in four step s with 40% overall yield from tryptophan methyl ester, which also opens a g eneral route for the preparation of the related 5-alkoxypyrazin-2(1H)-one 4 -oxides.