Divergent Syntheses of Euphorbia Diterpenoids: A Relay Rearrangement Strategy Triggered by Pyridinium Ring Contraction.

Euphorbia diterpenoids are a structurally diverse class of natural products renowned for their potent biological activities. Inspired by biosynthetic 1,2-migrations, yet deliberately departing from these pathways, we developed a synthetic strategy that provides collective access to multiple distinct skeletal families through relay rearrangements. Central to this approach is the photochemical ring contraction of pyridinium salts, followed by aziridine-mediated diversification, to construct highly functionalized cyclopentane cores. These intermediates could be transformed into the euphorstranoid scaffold via a retro-aldol/transannular aldol sequence that enables stereocenter inversion, and into the pepluanol scaffold through a rare cationic [3,4]-rearrangement. This unified strategy not only enables the total syntheses of (+)-resiniferatoxin, (-)-euphorstranoid B, and (+)-pepluanol A, but also establishes a modular platform for complex carbocycle assembly in terpenoid synthesis.