Total Synthesis of Matrine Alkaloids

The total synthesis of three diastereomeric matrine natural products is reported. The eight-step synthesis commences with simple acyclic precursors, forms all four rings of the tetracyclic natural product framework and forges ten of the twenty covalent bonds of the target structure. The chemical synthesis adopts an unprecedented strategy that encompasses both transform and stereochemical attributes. A cross-conjugated triene is positioned at the core of an acyclic branched structure, which collapses to the tetracyclic natural product framework through an orchestrated sequence of two intramolecular cycloadditions. A subsequent, late-stage hydrogenation is accompanied by strain-release redox epimerizations to deliver the three natural products. Semisynthetic manipulations of matrine provide access to ten additional natural products.