Abstract: Securines and securamines are alkaloids that contain a cis-enamide, neopentylic alkyl chloride, bromoimidazole, and a pyrroloindoline that was reported to exist in a solvent-dependent equilibrium with the corresponding indole–macrolactam isomer.  More complex isolates contain an oxidized hexacyclic structure, and varied bromination of the indoline that correlates with their cytotoxicity.  We recently developed 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, which may have bearing on the biosynthesis of the isolates.  The adaptation of this chemistry to the related spirocylic β-lactams known as chartellines will also be described.