Facile Synthesis and First Antifungal Exploration of Tetracyclic Meroterpenoids: (+)-Aureol, (−)-Pelorol, and Its Analogs

As an important bioactive molecular backbone, drimane
meroterpenoids
have drawn a great deal of attention from both pharmacologists and
chemists. Inspired by the prevalidated success of conformational restriction
in the discovery of novel pharmaceutical leads, two distinct tetracyclic
drimane meroterpenoids, (−)-pelorol and (+)-aureol, were synthesized
from the inexpensive starting material (−)-sclareol through
10 and 8 steps with 5.6% and 5.4% overall yield, respectively. The
mild conditions, operational facility, and scalability enabled the
expedient synthesis and biological exploration of not only natural
products themselves but also their mimics. The first agrochemical
exploration showed (−)-pelorol and (+)-aureol possessed good
antifungal activity against Rhizoctonia solani, with
EC50 values of 7.7 and 6.9 μM, respectively. This
revealed that tetracyclic drimane meroterpenoids are valuable models
for antifungal lead discovery.