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Evolution of the Total Synthesis of Gregatin A and Related Natural Products
1State Key Laboratory and Institute of Elemento-Organic Chemistry, Frontiers Science Center For New Organic Matter, College of Chemistry, Nankai University, Tianjin, China.
Abstract:
The gregatins constitute a distinctive family of fungal metabolites exhibiting notable phytotoxic and antimicrobial activities, which have attracted sustained interest from the synthetic community since their discovery. Despite their deceptively simple molecular architectures, the structural elucidation and asymmetric synthesis of gregatins have long remained challenging. Among them, gregatin A serves as the prototypical member and a proposed biosynthetic precursor to several dimeric congeners, including penicilfuranone A, asperones A and B, and citrifurans A and D. Over the past decades, remarkable progress has been achieved in the total and asymmetric synthesis of these compounds, reflecting the continuous evolution of synthetic strategies toward greater efficiency, selectivity, and biomimetic relevance. This review summarizes the methodological innovations and strategic advances that have shaped the total synthesis of gregatin A and its structurally related dimers, highlighting the broader conceptual evolution of asymmetric synthesis in complex natural product chemistry.
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