Divergent syntheses of complex Veratrum alkaloids.

The Veratrum alkaloids are a class of highly intricate natural products renowned for their complex structural and stereochemical characteristics, which underlie a diverse array of pharmacological activities ranging from anti-hypertensive properties to antimicrobial effects. These properties have generated substantial interest among both synthetic chemists and biologists. While numerous advancements have been made in the synthesis of jervanine and veratramine subtypes over the past 50 years, the total synthesis of highly oxidized cevanine subtypes has remained relatively scarce. Building on the efficiency of our previously developed strategy for constructing the hexacyclic carbon skeleton of the Veratrum alkaloid family via a stereoselective intramolecular Diels-Alder reaction and radical cyclization, here we show the development of a unified synthetic approach to access highly oxidized Veratrum alkaloids. This includes the total synthesis of (-)-zygadenine, (-)-germine, (-)-protoverine and the alkamine of veramadine A, by capitalizing on a meticulously designed sequence of redox manipulations and a late-stage neighboring-group participation strategy.