Saxitoxin (STX) is a complex guanidine-based alkaloid possessing potent biological activity. In fact, it is one of the most toxic non-protein substances known to Man. It has been estimated that a single dose of less than one milligram would prove fatal in humans, and on this basis is calculated to be 2000 times more toxic that sodium cyanide, and 100 times more poisonous than strychnine! With such high toxicity, it was hardly surprising, when in the 1950s, the CIA began to experiment with STX, its agents carrying the toxin in the form of suicide capsules, and for use in poison darts. In the UK, STX is one of only two natural toxins designated as a Schedule 1 Chemical Warfare Agent.

Our interest in STX derives from its involvement in incidences of paralytic shellfish poisoning (PSP) world-wide. This syndrome is mainly caused by consumption of shellfish which have become contaminated by STX as a result of feeding on a poisonous blue-green algal species, called Alexandrium catanella. The shellfish have a different nervous system to mammals and are not harmed, but instead concentrate the toxin in their tissue.

The algal species itself can grow incredibly fast when conditions are right, leading to spectacular phenomena like that shown above, which are called red tides (or harmful algal blooms). The red tide problem is becoming increasing prevalent, and has been blamed on polution in coastal areas, and also on farmland run-off into rivers and lakes. Most of the east coast of North America is now affected by harmful algal blooms (HABs) and also a substantial amount of the west coast. The effects of the toxins produced by these HABs have been suffered by people across the world, eg in Australia and also recently in an incident involving paralysis of swimmers off the coast of Swansea.

Our project involves the synthesis of STX using literature methods, and having obtained a sample of the toxin (and its precursors) we wish to study the modification of various parts of the molecule, to produce other natural toxins for use as internal standards.

The first synthesis of STX was completed by Kishi and co-workers at Harvard in 1977 (J. Am. Chem. Soc. 1977, 99, 2818), and then by Jacobi et al at Wesleyan University, Connecticut in 1984 (J. Am. Chem. Soc. 1984, 106, 5594). At present we are completing the Jacobi route to STX.