posted on 2022-05-11, 12:07authored byPo 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).