Total Synthesis of Matrine Alkaloids
Nicholas L. Magann, Erin Westley, Madison J. Sowden, Michael G. Gardiner, Michael S. Sherburn
Abstract
The total synthesis of three diastereomeric matrine natural products is reported. The 8-step synthesis commences with simple acyclic precursors, forms all 4 rings of the tetracyclic natural product framework, and forges 10 of the 20 covalent bonds of the target structure. A cross-conjugated triene is positioned at the core of an acyclic branched structure. This precursor collapses to the tetracyclic natural product framework through an orchestrated sequence of two separate intramolecular cycloadditions. A subsequent, late-stage hydrogenation is accompanied by strain-release redox epimerizations to deliver the three natural products. An unprecedented carba-analogue is prepared in the same way. Semisynthetic manipulations of matrine provide access to 10 additional natural products.