The cantharidin was first isolated by Robiquet, a French chemist in 1810. It has an important role in the ecology of different kinds of insects that use or produce it as a defense ability to preserve their eggs from predators. In the ancient world, the dried spanish flies had the reputation of aphrodisiac virtues . In fact, these supposed properties are not attested neither in theory nor in experimentation. The cantharidin seems to be a dangerous substance with the same toxicity as the most violent poisonus like strychnin.
Two insect-families belonging to beetles produce this substance : theMeloidae and the Oedemeridae. The first family groups together thousands species in which the Epicauta are the most widespread. Their most known representation is named Lytta Vesicatoria or Spanish fly. The opposite photography represents an example of this insect.
The cantharidin or 2, 3-dimethyl-7-oxabicyclo[2, 2, 1]heptane-2, 3-dicarboxylic anhydrid represented on the picture shown above, is an achiral compound. It has a plane of symmetry that goes through the middles of the bonds C2C3 and C5C6. It's a meso compound (2S, 3R).
Among the insects, the cantharidin is produced by the male and transfered to the female during the mating. The female will cover its eggs with this compound in a defense purpose. The complete mechanism of the biosynthesis is not known at the moment. But it is quite sure that it implicates reactions with as first compound a terpenic alcohol. A proof can be given with mass spectroscopy using the 14C, 3H, 18O isotopes .
|The farnesol represented on the picture is the (E, E)-3, 7, 11-triméthyldodeca-2, 6, 10-triene-1-ol. This is a sesquiterpenic alcohol. It is an intermediate in the biosynthesis of isoprenoïds.|
The farnesol is quite abundant in the nature. A lot of natural essences, like Ylang-ylang ones, contain this molecule.
The cantharidin inhibits the proteinphospatase 2A (PP2A), an enzyme that operates in the metabolism of glycogen .
The first effective synthesis of the cantharidin was made in 1951 by the American chemist G. Stork (born in Belgium)  and . The synthesis is completly linear and only uses classical reactions. It's a typical total synthesis of natural product dating from this period.
The Schenk's synthesis first uses a Diels-Alder reaction but here, the repulsions between the methyl groups don't exist and the equilibrium is favourable to the product .
Dauben is an American chemist in Berkeley University. He uses high pressure to realize a lot of synthesis. The Diels-Alder's reaction is realizable thanks to a pressure of 15 kbar. And then the synthesis of cantharidin necessitates only two steps , .
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 Ecology and Biosynthesis of Cantharidin and Palasonin
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