Synthesis of Anhydro-dc-Tetracyclic Saxitoxin Via a Photoinduced Cycloaddition

(+)-Saxitoxin, a potent and reversible blocker of voltage-gated sodium channels, has attracted considerable interests as a scaffold for the development of novel analogs. Here, we report the design and synthesis of a tetracyclic analogue featuring an additional <i>cis</i>-fused five-membered ring (C5-C6), constructed via a novel photoinduced radical cycloaddition reaction. This transformation efficiently established the quaternary carbon center at C5, which is difficult to access by conventional methods. Although the IC₅₀ values of two analogues against hNa_V1.4 showed a significant decrease in potency, this work introduces a new chemotype of saxitoxin, offering a foundation for future optimization efforts.