An oxidative photocyclization approach to the synthesis of skeletally-diverse Securiflustra securifrons alkaloids

Abstract

Securines and securamines are alkaloids that contain a cis-enamide, neopentylic alkyl chloride, bromoimidazole, and a pyrroloindoline that is in a reversible equilibrium with an indole. More complex isolates contain an oxidized hexacyclic structure, and varied bromination of the indoline that correlates with their cytotoxicity. Here we present a flexible route that provides access to the three skeletally-distinct classes of isolates and which will support elucidation of their structure–function relationships and biological target. The synthesis features the modular assembly of a macrolactam followed by a hydrochlorination cascade that introduces several critical substructures in a single step. The pyrroloindoline and hexacyclic skeletons were assembled by sequential oxidative photocyclizations of a precursor whose structure was elucidated by MicroED analysis, a burgeoning method for structure determination.