2007/07/21 by James J. Fleming, Matthew D. McReynolds, J. Du Bois · 1 citation
Environmental Science · Biochemistry, Genetics and Molecular Biology · Chemistry · #Marine Toxins and Detection Methods #Marine Sponges and Natural Products #Synthetic Organic Chemistry Methods
paper · doi:10.1021/ja071501o
openalex publication_date 2007/07/21 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/26
A stereoselective synthesis of the bis-guanidinium toxin (+)-saxitoxin (STX), the agent infamously associated with red tides and paralytic shellfish poisoning, is described. Our approach to this unique natural product advances through an unusual nine-membered ring guanidine intermediate 39 en route to the tricyclic skeleton that defines STX. The effectiveness of this strategy is notable, as only four steps are needed to transform 39 into the target molecule, including a four-electron alkene oxidation catalyzed by OsCl3. Construction of the critical monocyclic guanidine has been achieved through two channels, the first of which makes use of Rh-catalyzed C-H amination and highlights a novel class of heterocyclic N,O-acetals as iminium ion equivalents for crafting functionalized amines. A second route to 39 relies on a stereoselective acetylide dianion addition to a serine-based nitrone, thereby facilitating the preparation of STX in just 14 linear steps from commercial material.