Total Synthesis of Lyconesidine B: Approach to a Three-Dimensional Tetracyclic Skeleton of Amine-Type Fawcettimine Core and Studies of Asymmetric Synthesis

Lyconesidine B, isolated from Lycopodium chinense, is characterized by an oxygenated amine core and a trans-fused CD ring with a hydroxymethyl group on the axial position. Because the oxidation level of C13 of this alkaloid is different from other fawcettimine-type alkaloids, we investigated a suitable strategy for its synthesis. As a result, we established a synthetic route to the CD ring decahydroquinoline via cyclopropanation followed by ring-opening and reduction, and the AB ring tetracyclic core by ene-yne metathesis. In the ene-yne metathesis, the use of a quatemary ammonium salt solved the issues of the conformation of the substrate as well as the deactivation of the catalyst. The first total synthesis was achieved by stereoselective derivatization of the tetracyclic skeleton. In addition, we investigated the asymmetric cyclopropanation, which introduces an initial chiral center and was found to be effective for a Ru catalyst with vinyloxazoline-type ligands.

Automated summary

In this study, we successfully synthesized the core structure of Lyconesidine B and achieved stereoselective derivatization using different synthetic strategies. The synthesis of the tetracyclic core structure was achieved through cyclopropanation and ene-yne metathesis, while the asymmetric cyclopropanation introduced the initial chiral center.