Total synthesis of ageliferin via acyl N-amidinyliminium ion rearrangement

Abstract

Ageliferin is a marine natural product having antiviral and antimicrobial activities. These functions remain to be characterized at a molecular level. Ageliferin is also thought a biosynthetic intermediary linking oroidin type alkaloids to more complex polycyclic derivatives. This scenario has the amino tetrahydrobenzimidazole motif in ageliferin serving as a reduced progenitor of oxidized, ring-contracted spirocycles. Here we describe the reverse. Namely, a concise synthesis of ageliferin which features ring expansion of a spirocyclic precursor – itself derived from reduction. The pathway also provides access to unique isosteres of the axinellamine ring system, allowing new synthetic additions to the growing family of pyrrole/imidazole alkaloids.