Synthetic studies on pyrazinopsoralen

Abstract

The synthesis of pyrazinopsoralen, a monofunctional psoralen, was tried in this study. The study can be largely divided into the three synthetic strategies, one is through the intramolecular aromatic coupling reaction, another is the nucleophilic substitution of pyrazine ring with a organolithium compound and the third is the one which utilizes the intermolecular cross coupling reaction. Firstly, in the scheme through the palladium-catalyzed cyclization by dehydrohalogenation, the hydrolysis reaction of ester predominated over the desired coupling reaction. It seems to be due to the electron deficiency of pyrazine ring. In the trial of the nucleophilic substitution with a lithiated benzofuran moiety, a substitution did not occur at the desired ortho position of pyrazinyloxazoline but the para and meta substituted products were obtained. Therefore, it turned out to be improper in the synthesis of the target molecule. The connection of benzofuran moiety and pyrazine moiety could not be accomplished through the intermolecular cross Ullmann coupling reaction, probably, due to the steric hindrance by the ortho substituents in both rings.