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

Abstract

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.