Utilizing the intramolecular Fukuyama–Mitsunobu reaction for a flexible synthesis of novel heterocyclic scaffolds for peptidomimetic drug design

We report the synthesis of the novel scaffolds pyrazino[1,2-b]isoquinoline and pyrrolo[1,2-a]pyrazine displaying the somatostatin pharmacophores. Both classes of compounds contain a pyrazine heterocycle, which can be prepared in a straightforward manner utilizing an intramolecular Fukuyama–Mitsunobu reaction. As both the families derive from amino acids, they can be accessed in high optical purity.

Graphical abstractWe report the flexible syntheses of two scaffolds which derive from amino acids and can be decorated with a variety of pharmacophores while retaining full control over all stereocenters.Figure optionsDownload full-size imageDownload as PowerPoint slide