Synthesis of the C_(18)-Norditerpenoid Alkaloid Neofinaconitine: A Lesson in Convergent Synthesis Planning

摘要

Whether you are a seasoned veteran or just entering this fascinating world of molecules, chances are you would be astounded by the architectural intricacy and beauty of the norditerpenoid alkaloids that originate from the Aconitum and Delphinium species (Figure 1). Indeed, these natural products, not to mention their wide spectrum of pharmacological properties and the commercial success of lappaconi-tine (Allapinin, l), represent unprecedented challenges for the synthetic community to rival nature's sophisticated biosynthetic machinery. From both design and execution viewpoints, the unique carbon connectivities and oxygenation pattern within the hexacyclic cage-like scaffold demand innovative synthetic solutions to access the naturally occurring substance in its entirety, or even partial structural domains of this compound. After nearly four decades of synthetic investigations with seminal contributions from Wiesner and co-workers in the 1970s, a major milestone was recently achieved by a team of researchers at the Memorial Sloan-Kettering Cancer Institute with a remarkable total synthesis of neofinaconitine (8, Scheme 1).