Introduction
Chemical Properties
Synthesis
Derivatives
How it works
Symptoms
Treatment
Research
Reference
 
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- Derivatives -

       Tetrodotoxin (TTX) usually exists as a mixture of its derivatives. Due to variations in its
structure, some of these analogues are difficult to detect. It derivatives can be classified under
two categories íV naturally occurring and synthetic derivatives.

Naturally Occurring Derivatives
- Isolated from pufferfish, newts and frogs
- Detected by spectroscopic methods
Analogous of Tetrodotoxin has been identified by a combination of liquid chromatography
and electrospray ionization mass spectrometry. This method involves a reversed phase
column with long carbon chains and a mobile phase including an ion-pair reagent such
as ammonium heptafluorobutyrate.

Synthetic Derivatives (prepared by chemical modification of the structure)
There are various synthetic routes to obtain derivatives of Tetrodotoxin. One of the most
well-known techniques to achieve this is via the Pfitzner-Moffatt oxidation. 2 examples of
this method are shown below. Through the Pfitzner-Moffatt reaction, 5 derivatives were also
prepared by covalent attachment of either lysine, glycine, beta-alanine or ethylenediamine
to the oxidized toxin.

    Example 1: 2 step Pfitzner-Moffatt oxidation

    Step 1
    Reagents : H2O2, FeSO4.7H2O
    Solvents : H2O, AcOH

    Step 2
    Reagents : NaBT4
    Solvents :
    AcOH,H2O,MeCN

    Example 2: 1 step Pfitzner-Moffatt oxidation


    Reagents : DMSO, H3PO4, DCC
    Solvents : CF3COOH

Besides the Pfitzner-Moffatt oxidation, TTX derivatives can also be obtained by other methods.
The diagram below shows 4 ways of synthesizing 7 different TTX derivates, and their respective yields.

"Synthetic TTX derivatives"
A, 11-oxoTTX and TTX-11-carboxylic acid; B, 11-norTTX-6,6-diol, 11-norTTX-6(S)-ol,
and 11-norTTX-6(R)-ol; C, tetrodonic acid; D, TTX-8-O-hemisaccinate.
- http://jpet.aspetjournals.org/cgi/content/full/289/3/1688

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