Studies Directed Toward the Total Synthesis of dcSTX, LWTX4, GC toxins

Abstract

Paralytic Shellfish Toxins (PSTs), known as STX and its derivatives, are a group of naturally occurring marine biotoxins produced by certain genera of marine dinoflagellates, such as Alexandrium, Gymnodinium and Pyrodinium. PSTs usually act as selective blockers of the voltage-gated sodium channel (NaV) in neurons, resulting interruption of signal transfer in the nervous system and eventually paralysis. The powerful neurological toxicity of PSTs has attracted interests from many synthetic chemists, leading to development of various total syntheses. STX and its derivatives are chemically featured as a unique tricyclic skeleton, which contains cyclic guanidine moieties. In this report, we proposed a convergent synthetic pathway to STX derivatives, including rare toxins such as LWTXs and GC toxins, utilizing a modified Looper’s synthesis. Our synthesis could be roughly divided into three stages, including a fragment coupling, cyclization, and derivatization. Qualitative and quantitative analyses of the synthetic STX derivatives were conducted under the official liquid chromatography post-column oxidation-fluorescence detector (LCPCOX- FLD) conditions, according to AOAC Method-OMA 2011.02, to examine their usability and effectiveness as analytical reference materials. We envision that our effort would provide a sufficient amount of the rare toxins to elucidated detailed effects of the toxins on marine ecosystem and unexplored biological properties.