Total synthesis of (−)-flueggenine A and (−)-15′-<i>epi</i>-flueggenine D

Securinega alkaloids, known for their unique structures and neuroplasticity-inducing potential, are promising candidates for treating neurodegenerative diseases such as depression and substance use disorders (SUD). Herein, we delineate the total synthesis of two dimeric Rauhut-Currier (RC) reaction-based securinega alkaloids, (-)-flueggenine A and (-)-15'-<i>epi</i>-flueggenine D. The key step involved a novel reductive Heck dimerization strategy, utilizing a silyl-tethered enone coupling partner to ensure the desired reactivity and stereoselectivity. This dimerization method, combined with established chemistry explored en route to (-)-flueggenines C and D, offers a comprehensive synthetic approach for accessing all known RC-based oligomeric securinega alkaloids.