Rapid Construction of Tricyclic Carbon Framework for Convergent Synthesis of Manginoid Meroterpenoids

Manginoid meroterpenoids are a unique class of monoterpene-shikimate conjugated meroterpenoids. Nine analogues, designated manginoids A-I, were previously isolated from fungi. All analogues feature a common 3',7'-dimethylspiro[cyclohexane-1,5'-indene] skeleton, representing an unprecedented structural motif in natural product chemistry. In this study, we developed a synthetic strategy for the rapid construction of the core skeleton of manginoids for efficient convergent synthesis and analogue preparation. This methodology involves a two-step sequence: the carbon-carbon bond formation with Knoevenagel condensation and sequential 1,4-reduction, followed by the cyclization. This study demonstrates a concise approach to construct various cores of manginoid meroterpenoids in short steps, facilitating the efficient synthesis of natural manginoid meroterpenoids.