An easier approach to recreate the powerful nerve-blocking molecule saxitoxin found in shellfish

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"Chemists have long been fascinated and frustrated by saxitoxin: a molecule that causes temporary paralysis by blocking the electrical signals that nerve cells (neurons) use to activate muscle, and which accumulates in shellfish like clams, oysters and scallops. ...

Now [early Dec 2025], scientists ... report a streamlined approach to synthesize saxitoxin and related molecules (known as analogs) in the lab. They combined a synthetic chemical route with an engineered enzyme to make the molecule in less than 10 steps, compared to 11–21 in earlier approaches.

Reducing the total step count is a major advance in synthesis because each step typically lowers yield while increasing cost and time; a shorter route can deliver much more material with far fewer resources. ...

Published in Nature, the research team’s tactic relies on two methods.

The first is radical cross-coupling: a technique that uses highly reactive molecular fragments, called radicals, to form bonds that are difficult or even impossible to create with traditional reactions.

The second method is biocatalysis, where enzymes—proteins that speed up reactions—carry out chemical steps that would otherwise be difficult. ..."

From the abstract:

"Saxitoxin (STX, 1), a potent neurotoxin from shellfish, first isolated in 1957, offers immense pharmaceutical potential owing to its interaction with voltage-gated sodium channels, which are ubiquitously present in all excitable cells of the central and peripheral nervous system.

Hundreds of studies towards its synthesis have been disclosed so far, yet a fully modular and scalable approach to the family remains elusive.

Here we show how a tactical combination of radical retrosynthesis, biocatalysis and C–H functionalization logic can be used to solve this problem, resulting in a scalable approach to the STX family in fewer than ten steps, including the first total synthesis of neosaxitoxin (neoSTX), a hydroxylated naturally occurring STX analogue previously under clinical investigation.

The modular nature of the synthesis enables access to diverse analogues that were previously inaccessible and have now been evaluated through electrophysiological assays for biological activity."

An easier approach to recreate the powerful nerve-blocking molecule found in shellfish | Scripps Research "A Scripps Research-led study resolves the challenge of synthesizing saxitoxin, paving the way for new possibilities in pain management."

Scalable total synthesis of saxitoxin and related natural products (no public access)

Scalable, Convergent Total Synthesis of (+)-Saxitoxin and Related Natural Products (working paper, open access)

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