BACKGROUND AND PURPOSEThe development of subtype-selective ligands to inhibit voltage-sensitive sodium channels (VSSCs) has been attempted with the aim of developing therapeutic compounds. Tetrodotoxin (TTX) is a toxin from pufferfish that strongly inhibits VSSCs. Many TTX analogues have been identified from marine and terrestrial sources, although their specificity for particular VSSC subtypes has not been investigated. Herein, we describe the binding of 11 TTX analogues to human VSSC subtypes Na v 1.1-Na v 1.7. EXPERIMENTAL APPROACHEach VSSC subtype was transiently expressed in HEK293T cells. The inhibitory effects of TTX analogues on each subtype were assessed using whole-cell patch-clamp recordings.

The first total synthesis of chiriquitoxin, the most structurally complex analogue of tetrodotoxin isolated from a Costa Rican dart frog, has been accomplished from a newly designed intermediate for a variety of tetrodotoxin derivatives. The synthesis includes the third total synthesis of tetrodotoxin in this laboratory, and its intermediate was transformed into chiriquitoxin by a stereocontrolled aldol reaction with a D-camphor-derived lactone for installation of the unique side chain, and a new deprotection of methylthiomethyl (MTM) ether by using a Pummerer rearrangement.

5,6,11-Trideoxytetrodotoxin, a naturally occurring analog of tetrodotoxin, was synthesized from a synthetic intermediate of 5-deoxytetrodotoxin by continuous radical deoxygenation of two hydroxy groups at the C-6 and C-11 positions.

Several polyclad flatworm species are known to contain high levels of tetrodotoxin (TTX), but currently TTX-bearing flatworms seem to be restricted to specific Planocera lineages belonging to the suborder Acotylea. During our ongoing study of flatworm toxins, high concentrations of TTXs were detected for the first time in the flatworm Prosthiostomum trilineatum, suborder Cotylea, from the coastal area of Hayama, Kanagawa, Japan. Toxin levels were investigated by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), revealing that this species contains comparable concentrations of toxins as seen in planocerid flatworms such as Planocera multitentaculata. This finding indicated that there may be other species with significant levels of TTXs. The distribution of TTXs among other flatworm species is thus of great interest.

Redox-active organic molecules are promising candidates for next-generation electrode materials. Nevertheless, finding low-molecular-weight organic materials with a long cycle life remains a crucial challenge. Herein, we demonstrate the application of tetrathiafulvalene and its vinyl analogue bearing triphenylamines as long-cycle-life electrodes for lithium-ion batteries (LIBs). These molecules were successfully synthesized using palladium-catalyzed C–H arylation. Electrochemical analysis revealed that a polymer formed on the electrode. LIBs comprising these molecules exhibited noteworthy charge–discharge properties with a long cycle life (the capacity after 100 cycles was greater than 90% of the discharge capacity in the third cycle) and a high utilization ratio (approximately 100%). “In-cell” polymerization during the first charge process is considered to contribute to the effect. This study indicates new avenues for the creation of organic materials for rechargeable batteries.