title: 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.
authors: Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiya, Aoba-ku, Sendai 981-8555 (Japan).
authors: Shigeki
authors: S
authors: Tsuchiya
authors: Yuko
authors: Y
authors: Cho
authors: Keiichi
authors: K
authors: Konoki
authors: Kazuo
authors: K
authors: Nagasawa
authors: Yasukatsu
authors: Y
authors: Oshima
authors: Mari
authors: M
authors: Yotsu-Yamashita
mesh_terms: D000818:Animals; D002384:Catalysis; D002460:Cell Line; D003500:Cyclization; D004141:Dinoflagellida / Q000737:chemistry; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry; D008387:Marine Toxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D010084:Oxidation-Reduction; D012530:Saxitoxin / Q000737:chemistry*; D012758:Shellfish / Q000032:analysis; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D007093:Imidazoles; D008387:Marine Toxins; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012530:Saxitoxin; C014973:2-aminoimidazole; D019791:Guanidine
keywords: biosynthesis; cyclization; natural products; palladium; toxicology