American Chemical Society
ol2c00961_si_001.pdf (10.74 MB)

Enantioselective Total Synthesis of (+)-Pepluanol A

Download (10.74 MB)
journal contribution
posted on 2022-05-11, 12:07 authored by Po Yuan, Tanja Gaich
Herein, we report an enantioselective and convergent total synthesis of (+)-pepluanol A, a structurally intriguing Euphorbia diterpenoid natural product featuring a 5/6/7/3-fused tetracyclic skeleton, from known building blocks in 11 steps. The successful strategy relies on a phenyl selenide-mediated Morita–Baylis–Hillman type reaction as a connective step, forging the precursor for the key intramolecular Diels–Alder reaction to construct the congested 5/6/7-tricyclic framework. A diastereoconvergent cascade starting with an acid-induced removal of the C1-MOM protecting group followed by a retro-aldol/aldol reaction resulted in the formation of a single diastereomer. This stereoconvergency allowed for the successful substrate-controlled diastereoselective cyclopropanation of an advanced intermediate to establish the full carboskeleton of (+)-pepluanol A (1).