Synthesis of the insect feeding deterrent peramine via Michael addition of a pyrrole anion to a nitroalkene

Abstract

A total synthesis of peramine (1), the major insect feeding deterrent isolated from perennial ryegrass (Lolium perenne L.) infected with the endophytic fungus Acremonium lolii is reported. The key step involves the Michael addition of the potassium salt of methyl pyrrole-2-carboxylate (3) to the nitroalkene (4) providing access to a 3-substituted pyrrolo[1,2-a]pyrazin-1 (2H)-one (10). Displacement of the allylic bromide (11) by cyanomethyl cuprate provided the methodology for introducing the desired monosubstituted guanidino group via the nitrite (12).