Synthesis of a Tricyclic Bisguanidine Compound Structurally Related to Saxitoxin and its Identification in Paralytic Shellfish Toxin-Producing Microorganisms

We recently reported the chemical synthesis and identification of the genetically predicted biosynthetic intermediates of saxitoxin (STX), including a 2‐aminoimidazole‐bearing monoguanidine compound (Int‐C′2) in two paralytic shellfish toxin (PST)‐producing microorganisms. In this study, we achieved the direct conversion of Int‐C′2 into a tricyclic bisguanidine compound (called Cyclic‐C′), which is structurally related to STX, through oxidative intramolecular guanidine transfer to 2‐aminoimidazole catalyzed by Pd/C under basic conditions in air. By using HPLC‐MS analysis, Cyclic‐C′ was also identified in the PST‐producing microorganisms, suggesting that Cyclic‐C′ is either another biosynthetic intermediate or a shunt product of PSTs. In addition, a weak inhibitory activity of Cyclic‐C′ to the voltage‐gated sodium channels was detected by using a cell‐based assay. You know that you′re toxic: Direct conversion of Int‐C′2, a biosynthetic intermediate of saxitoxin (STX), into a tricyclic bisguanidine compound (Cyclic‐C′), which is structurally related to STX, was achieved through oxidative cyclization catalyzed by Pd/C under basic conditions in air (see scheme). By using HPLC‐MS analysis, Cyclic‐C′ was also identified in the paralytic shellfish toxin (PST)‐producing microorganisms, suggesting that Cyclic‐C′ is involved in biosynthesis of PSTs.