Synthesis of 2-Amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine

Abstract

2-Amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine (2), a precursor of Watasenia preluciferin (coelenterazine) (1), is widely distributed in marine bioluminescent animals. It was prepared from p-hydroxyphenylglyoxal aldoxime (5) in two steps; by condensation with α-aminophenylpropiononitrile in the presence of TiCl₄ in pyridine, followed by reduction of the resulting N-oxide (6) with Zn–AcOH in CH₂Cl₂ and produced 2, with an 89% overall yield. This procedure was linked with the facile one-step preluciferin synthesis reported in the previous paper. Thus, Watasenia preluciferin (1), frequently required for various chemiluminescent and bioluminescent studies, was coveniently synthesized in three steps from 5, with a 56% overall yield, overcoming the difficulty of obtaining it from natural sources.