Expediently Scalable Synthesis and Antifungal Exploration of (+)-Yahazunol and Related Meroterpenoids

The efficient synthesis and antifungal
exploration of (+)-yahazunol
and related natural products are described. Central to this strategy
is the Barton decarboxylative coupling, comprising a one-pot radical
decarboxylation and quinone addition cascade. The scalable synthesis
of (+)-yahazunol was accomplished in five longest linear sequences
(LLS) starting from commercially available and inexpensive (−)-sclareol.
The divergent translational potential of (+)-yahazunol was demonstrated
by the expedient preparation of (−)-zonarone, (−)-isozonarone,
(−)-zonarol, (−)-isozonarol, (+)-chromazonarol, and
(+)-yahazunone. This approach also enables the formal synthesis of
puupehenol, puupehedione, and hongoquercin A. Antifungal evaluation
was performed, and this represents the first biological profiles for
(+)-yahazunone, (+)-8-O-acetylyahazunone, and (+)-8-O-acetylyahazunol. (+)-Chromazonarol and (+)-yahazunone
are promising candidates against Sclerotinia scleotiorum, with EC50 values of 24.1 and 28.7 μM, respectively,
demonstrating advantages over the original model (DM) and synthesized
heterocyclic mimic (3a) of meroterpenoids. This will
favor the establishment of a chemical repertoire in the management
of different plant diseases.