Discovery and synthesis of flueggeacosines D-F and securingine J.

Abstract

Securinega alkaloids constitute a structurally diverse class of natural products with intriguing architectures and biological activities. Herein, we report the discovery of four new Securinega alkaloids, flueggeacosines D-F and securingine J, from Flueggea suffruticosa. Flueggeacosines D and E possess dimeric frameworks incorporating a benzoquinolizidine motif derived from allosecurinine backbone. A concise synthetic strategy combining TBADT-catalyzed radical hydroacylation and Mo(CO)₆-mediated reductive rearrangement enables efficient access to these complex alkaloids. Our synthetic approach also realizes a synthesis-based natural product anticipation predicting and confirming the existence of flueggeacosine F and securingine J in F. suffruticosa. Furthermore, oxidative rearrangements of flueggeacosine A furnish flueggeacosines D and F, supporting a plausible biosynthetic linkage. These findings establish a unified route to oxidized dimeric Securinega alkaloids and demonstrate the synergy of synthesis and biosynthetic reasoning in natural product discovery.