Modification of tetrodotoxin with succinic anhydride

With an aim toward the synthesis of physiologically active derivatives of the powerful neurotoxin tetrodotoxin and the use of such derivatives in biochemical studies of the molecular makeup of the tetrodotoxin binding site in nerve, the modification of tetrodotoxin with succinic anhydride has been examined. A new toxin derivative, 11-succinylanhydrotetrodotoxin, is described which contains a remote carboxylic acid grouping suitable for subsequent modification or attachment to an affinity column. High voltage electrophoresis and radiochemical techniques served to establish the purity of the derivative and its relative toxicity, namely, 0.4% that of tetrodotoxin (frog nerve assay). Structure assignment was made on the basis of the FT 100 MHz nmr spectrum.