Bioinspired Divergent Oxidative Cyclization of Strictosidine and Vincoside Derivatives: Second Generation Enantioselective Total Synthesis of (–)-Cymoside

We report our second generation synthesis of (–)-cymoside as well as the formation of a new hexacyclic-fused furo[3,2- b ]indoline framework. After a Pictet-Spengler condensation between secologanin tetraacetate and tryptamine, the course of the cyclization of the 7-hydroxyindolenine intermediate generated by oxidation with an oxaziridine, depends on the stereochemistry of the 3-position. The 3 -(S)- strictosidine stereochemistry delivered efficiently the scaffold of cymoside via intramolecular coupling with the C16-C17 enol ether, while the 3 -(R)- vincoside stereochemistry directed towards the reaction with the C18-C19 terminal alkene and the formation of the unexpected caged compound.