Divergent Syntheses of the Euphorbia Diterpenoids Pepluanol A and Pepluacetal

Pepluanol A (1) and pepluacetal (2) belong to a structurally unique class of pepluanol-type Euphorbia diterpenoids, exhibiting immunosuppressive activity via targeting K_v1.3 channels. Herein, we report a divergent synthetic strategy that enables efficient and concise total syntheses of both 1 and 2 from a common advanced intermediate. The synthesis of pepluanol A (1) features an intramolecular Diels-Alder reaction to accomplish the [4 + 2] type cycloaddition for framework construction, whereas the synthesis of pepluacetal (2) is centered on a photoinduced intramolecular [2 + 2] cycloaddition as the key step. Both routes proceed with high stereoselectivity and synthetic efficiency. Further biological evaluation revealed that these diterpenoid natural products and derivatives possess antipulmonary fibrosis activity.