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 sp³-sp² 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.