A Unifying Stereochemical Analysis for the Formation of Halogenated C15-Acetogenin Medium-Ring Ethers From Laurencia Species via Intramolecular Bromonium Ion Assisted Epoxide Ring-Opening and Experimental Corroboration with a Model Epoxide

A unifying stereochemical analysis for the formation of the constitutional isomeric halogenated C(15)-acetogenin medium-ring ether natural products from Laurencia species is presented, where an intramolecular bromonium ion assisted epoxide ring-opening reaction of enantiomerically pure epoxides can account for ring-size, the position of the halogen substituents, and relative and absolute configurations of the known natural products. Experimentally, a model epoxide corroborates the feasibility of this process for concurrent formation of 7-, 8- and 9-ring ethers corresponding to the halogenated medium-ring ethers of known metabolites from Laurencia species.