Demethylative Lactonization Provides a Shortcut to High-Yielding Syntheses of Lamellarins.

Modular gram-scale syntheses of the trimethyl ethers of lamellarins G () and D () were achieved from readily accessible precursors in the highest overall yields reported to date (, six steps, 82%; , seven steps, 86%). A novel demethylative lactonization between an aryl methyl ether and a neighboring carboxylic acid was developed for creating the chromenone unit of the targets to avoid the need for additional protection and deprotection steps. The central pyrrole core was constructed in a late-stage [4 + 1] condensation between ethyl bromoacetate and an enaminone possessing the remaining components of the lamellarin skeleton. Exhaustive demethylation of both permethyl ethers and gave the polyphenolic natural lamellarins A4 () and H (), respectively.