Practical Synthesis and Antifungal Investigation of Drimane Meroterpenoids Enabled by Nickel-Catalyzed Decarboxylative Coupling

Drimane meroterpenoids have drawn increasing attention
in the discovery
of novel pharmaceutical leads owing to their structural diversity
and bioactivity variation, but further development is significantly
impeded by the lack of an efficient modular route of preparation.
A nickel-catalyzed decarboxylative cross-coupling paradigm has been
established to expeditiously access a constellation of drimane meroterpenoids.
The redox-active drimane precursor is a bench-stable coupling partner
and is easily available from the inexpensive feedstock sclareol. This
transformation features the tolerance of challenging functional groups
(phenol, aldehyde, ester, etc.) and mild conditions with a low-cost
nickel catalytic system. The synthetic utility is further highlighted
by the direct scalable synthesis of challenging drimane meroterpenoids
as diversifiable advanced intermediates for late-stage functionalizations.
This method facilitated antifungal investigations and culminated in
the discovery of compounds C8 and C3 as
new antifungal leads against Rhizoctonia solani,
with EC50 values of 4.9 and 7.2 μM, respectively.