K. Matoba et al., Process research and protecting groups: Practical synthesis of substitutedpyrazine N-oxide derivatives, J SYN ORG J, 57(5), 1999, pp. 407-414
An efficient and practical synthetic route to OPC-15161 (1), a novel inhibi
tor of superoxide anion generation, is described. Intensive survey on pyraz
ine ring manipulation has led to the development of multi-kilo synthetic pa
thway, in which beneficial use of a nitrogen protecting group is the key to
the problematic cyclization and O-methylation process, both being carried
out in one-pot operation. Thus, the synthesis proceeds in 40% overall yield
in four steps from tryptophan methyl ester with simple operation and witho
ut chromatographic purification, which also opens a general route for the p
reparation of related 5-alkoxypyrazin-2(1H)-one 4-oxide such as emeheterone
.