SYNTHESIS OF 2,5-DIOXYGENATED PYRAZINE 4-OXIDES - TOTAL SYNTHESIS OF A NEW INHIBITOR OF SUPEROXIDE ANION GENERATION, OPC-15161

The total synthesis of OPC-15161 1, a new inhibitor of superoxide anio n generation, is described in full. Three approaches, routes A-C, have been investigated focusing on the pivotal structure 2,5-dioxygenated pyrazine 4-oxide. Among them, route A led to the total synthesis of 1. That is, the key precursor, 5-hydroxypyrazin-2(1H)-one 4-oxide 7 has been prepared from tryptophan methyl ester 2 in three steps, and direc t methylation of the 5-hydroxy group of 7 or three-step methylation vi a the 2-O-Boc derivative 10 afforded 1 in 9.9-10.6% overall yields.