An "Inside-Out" Strategy Enables a 14-Step Total Synthesis of Hispidospermidin.

ABSTRACT: Traditionally, a retrosynthesis aims to disconnect a molecular target into simpler precursors as quickly as possible, prioritizing the early deconstruction of primary contributors to the molecule's overall structural complexity (i.e., primary complexity elements). The complementary approach, which rapidly constructs complexity early in the forward synthesis, is much less common. Herein, we report a 14-step protective group-free total synthesis of the polycyclic sesquiterpenoid alkaloid hispidospermidin, which exploits an early-stage complexity-generating bicycle formation to forge the carbon skeleton, followed by subsequent peripheral functionalizations. Specifically, a key Giese conjugate addition of a bridgehead radical established the quaternary center, and a novel isomerization was dis

SUBMITTER: Amber C 

PROVIDER: S-EPMC12848721 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature