Total Synthesis of 11‐Saxitoxinethanoic Acid and Evaluation of its Inhibitory Activity on Voltage‐Gated Sodium Channels

11‐Saxitoxinethanoic acid (SEA) is a member of the saxitoxin (STX) family of paralytic shellfish poisons, and contains an unusual C−C bond at the C11 position. Reported herein is a total synthesis of SEA. The key to our synthesis lies in a Mukaiyama aldol condensation reaction of silyl enol ether with glyoxylate in the presence of an anhydrous fluoride reagent, [Bu 4 N][Ph 3 SnF 2 ], which directly constructs the crucial C−C bond at the C11 position in SEA. The Na V Ch‐inhibitory activities of SEA and its derivatives were evaluated by means of cell‐based assay. SEA showed an IC 50 value of (47±12) n m , which is approximately twice as potent as decarbamoyl‐STX (dcSTX).