Secupyritines A‒C, Three Natural Propellane Securinega Alkaloids: Structure Elucidation and Total Synthesis Based on Biogenetic Building Blocks

Abstract Secupyritines A‐C are unique polycyclic Securinega alkaloids isolated from medicinal plant Flueggea suffruticosa . They feature a distinctive 6/6/6/5/6 fused pentacyclic ring system with a highly strained 2‐oxa‐6‐aza[4.4.3]propellane core. Their structures with absolute configurations were elucidated through a comprehensive approach involving nuclear magnetic resonance (NMR) spectroscopy, single‐crystal X‐ray crystallography, electronic circular dichroism (ECD) calculations, and total synthesis. The total synthesis of secupyritines A‐C was achieved in 14 or 16 steps, employing a synthesis strategy based on biogenetic building blocks. Key elements of the synthetic procedures include a vinylogous Mannich‐type reaction to construct the sp 3 ‐sp 2 attached‐ring system, a Suzuki coupling reaction to build the piperidine ring, and an intramolecular aza ‐Michael addition reaction to establish the propellane skeleton. Formal asymmetric synthesis of secupyritines A‐C was also presented.