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Batrachotoxin total synthesis

18 November 2016 - Total Frogs

dubois1026.PNGSo why does my Twitter feed all of a sudden have these little yellow frogs? Must be an all-important new batrachotoxin (BTX) total synthesis? Yes, there it is: a Justin du Bois report in Science (DOI) about the compound made infamous by the poison dart frog! The toxicity of the compound excreted by this animal is legendary, the lethal dose is just 2 microgram per Kg. The novel total synthesis is one thing, the intriguing history of the discovery is another. As written up by Garraffo and Spande in 2009 (DOI) two individuals, called Daley and Latham where on to the compound back in the sixties and collected a large number of frogs in the Columbian jungle for extraction. The procedure required skinning and Latham suffered partial-hand paralysis for some time to do so without using gloves. Eventually 5000 skins provided 11 mg of BTX via column chromatography. Now these frogs have become scarce and frogs kept in captivity do not contain BTX (in the wild they get it from a certain food source) so synthetic BTX seems the only way forward to a fresh supply. Du Bois at al. did the job in 22 steps or so starting from the Hajos-Parrish ketone with a 2 mg final yield. Does not sound like a lot but the quantity can easily kill 500 mice. The safety instructions in the supplementary info are surprisingly relaxed. Make sure to wear the gloves.