A bioinspired cyclization toward koumine and gelsemine

Koumine and gelsemine, two principal indole alkaloids isolated from Gelsemium, have emerged as appealing targets in recent decades because of their dazzling structures and intriguing bioactivities. In addition to a number of reported total syntheses, insight into hypothesized biosynthetic pathways to these products has inspired bond disconnections in retrosynthetic analyses, resulting in several intriguing synthetic routes. In this perspective, selected examples featuring the key bioinspired steps toward koumine and gelsemine are discussed. Liu's biomimetic synthesis of koumine via Friedel-Crafts-type cyclization was seminal for succeeding synthetic designs by other practitioners. For the homologous structure gelsemine, bioinspired studies enable the formation of a key spiroxindole via different approaches. Although the ene-type cyclization to form the C6-C20 bond in the proposed biosynthesis of gelsemine remains unexplored, we anticipate an aza-Prins cyclization initiated by the activated imine intermediate to be viable for the future exploration of biomimetic synthesis.