Synthesis of a tricyclic bisguanidine compound structurally related to saxitoxin and its identification in paralytic shellfish toxin-producing microorganisms.

Abstract

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.