Saxitoxin analogs

The biosynthesis of two major classes of red tide toxins, saxitoxin analogs and brevetoxins, have been studied. It was shown that saxitoxin is biosynthesized from arginine, acetate, and methionine methyl group. Brevetoxins were shown to be unique polyketides, which are probably biosynthesized from dicarboxylic acids. Some details of the biosynthetic mechanism have been elucidated. 

In the above-mentioned work, DeU Aversano et al. [45] also carried out an exhaustive description about the fragmentation pattern of several saxitoxin analogs using tandem mass spectrometry, indicating that for some PSP toxins the mass spectra vary strongly with instrument type. Table 8.3 shows the typical fragment ions monitored for PSP toxin analysis by LC-MS. 

Yotsu-Yamashita M, Kim YH, Dudley SC Jr, Choudhary G, Pfahnl A, Oshima Y, Daly JW (2004) The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki. Proc Natl Acad Sci USA 101 4346-4351... 

Shimizu, Y., M. Kobayashi, A. Genenah, and Y. Oshima Isolation of Side-Chain Sulfated Saxitoxin Analogs — Their Significance in Interpretation of the Mechanism of Action. Tetrahedron, in press. 

A similar observation in the dinoflagellate Alexandrium tamarense and the mussels Mytilus edulis and Mytilus trossulus was made after an intense bloom of the dinoflagellate in Nova Scotia, Canada, in Jrme 2000. Four new saxitoxin analogs, M1-M4, were extracted and characterized (Dell Aversano et al, 2008). 

The paralytic shellfish toxins (PSTs Fig. 5.2a) include saxitoxin (STX) as well as STX analogs such as neo-saxitoxin (neo-STX), gonyautoxin (GTX), and the decar-bamoyltoxins (Sivonen and Jones 1999). These molecules are of particular concern in marine systems, where they have been implicated in human deaths following the consumption of contaminated seafood (Van Dolah 2000). The causative agents in those cases are several genera of marine dinoflagellates that are common components of red tides (e.g., Alexandrium sp. Homer et al. 1997 Van Dolah 2000). 

Fig. 6.8 Naturally occurring analogs of saxitoxin produced by both cyanobacteria and dinoflagellates. STX and neoSTX differ in the hydroxylation of N-1. DecarbamoylSTX (dcSTX) lacks the carbamoyl uniton 0-18.

Wiese M, D Agostino PM, Mihali TK, Moffitt MC, Neilan BA (2010) Neurotoxic alkaloids saxitoxin and its analogs. Mar Drugs 8 2185-2211. doi 10.3390/md8072185... 

When the structure of gonyautoxin-VIII (10) was established (vide infra), it was immediately suspected that (7) and (8) were analogous carbamoyl-N-sulfated derivatives of saxitoxin and neosaxitoxin 8, 60—63). The structures were confirmed by partial synthesis of (7) and (8) from de-carbamoylsaxitoxin (26) and decarbamoylneosaxitoxin (38) respectively on treatment with chlorosulfonyl isocyanate in formic acid 60) according to a previously reported procedure 64). 

Fifty-seven analogs of saxitoxin are mentioned in Wiese et al. (2010). 

Jang, J. and Yotsu-Yamashita, M. (2006) Distribution of tetrodotoxin, saxitoxin, and their analogs among tissues of the puffer fish Fugu pardalis. Toxicon, 48, 980-987. 

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