MIT unraveling secrets of red tide(tory and many came to believe that the ...)

"A lot of people thought that this type of cascade may be impossible," said Jamison. "Because Nakanishi's hypothesis accounts for so much of the complexity in these toxins, it makes a lot of sense, but there hasn't really been any evidence for it since it was first proposed."

Jamison and Vilotijevic's work offers the first evidence that Nakanishi's hypothesis is feasible. Their work could also help accelerate drug discovery efforts. Brevenal, another dinoflagellate product related to the red tide toxins, has shown potential as a powerful treatment for cystic fibrosis (CF). It can also protect against the effects of the toxins.

"Now that we can make these complex molecules quickly, we can hopefully facilitate the search for even better protective agents and even more effective CF therapies," said Jamison.

Until now, synthesizing just a few milligrams of red tide toxin or related compounds, using a non-cascade method, required dozens of person-years of effort.

The new synthesis depends on two critical factors-giving the reaction a jump start and conducting the reaction in water.

Many red tide toxins possess a long chain of six-membered rings. However, the starting materials for the cascades, epoxy alcohols, tend to form five-membered rings. To overcome that, the researchers attached a "template" six-membered ring to one end of the epoxy alcohol. That simple step effectively launches the cascade of reactions that leads to the toxin chain, known as a ladder polyether.

"The trick is to give it a little push in the right direction and get it running smoothly," said Jamison.

The researchers speculate that in dinoflagellates, the initial jump start is provided by an enzyme instead of a template.

Conducting the reaction in water is also key to a successful synthesis. Water is normally considered a poor solven
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