Synthesis of Alstoscholarisines A–E, Monoterpene Indole Alkaloids with Modulating Effects on Neural Stem Cells

A divergent synthetic strategy has been developed for stereoselective total syntheses of alstoscholarisines A–E, monoterpenoid indole alkaloids which are modulators of adult neuronal stem cells. A pivotal step includes an intermolecular Michael addition of an indole-2-acetic acid methyl ester enolate to an α,β-unsaturated N-sulfonyllactam to form the C15, C16 bond of the alkaloids. Other features of the strategy involve a selective partial reduction of an intermediate N-sulfonyllactam followed by cyclization to a bridged aminal system that serves as a key precursor for all five of the alkaloids as well as the use of an allyl group as a masked aldehyde equivalent.