Chiroptical analysis of marine sponge alkaloids sharing the pyrrolopyrazinone core.

Abstract

A systematic experimental study has been conducted on the chiroptical properties of bi- and tricyclic pyrrolopyrazinones, which occur as the core in a variety of marine pyrrole-imidazole alkaloids, such as the immunosuppressive palau'amine. On the basis of the chiral-pool synthesis of conformationally fixed dipyrrolopyrazinones, it was possible to predict the CD spectrum of (-)-dibromophakellin above 240 nm. 2,2,2-Trifluoroethanol was identified as a superior solvent for this analysis. Positive Cotton effects at 250 nm can be used to determine the helicity of dibrominated pyrrolopyrazinones, while the intensity of the Cotton effect at 285 nm is governed by the relative stereochemistry. The influence of bromination of the pyrrole ring also becomes predictable. One of the tricycles can be considered as "conformationally frozen longamide A". Our study also gives the first comparative Röntgen analyses of diastereomeric Mosher esters of N,O-hemiacetals, with the results underlining the fact that caution is advised in the application of the advanced Mosher method.