Gephyrotoxin is a naturally occurring product that stems from the Colombian tropical frog '' Dendrobates histrionicus''. It is a member of the class of compounds known as
histrionicotoxin
Histrionicotoxins are a group of related toxins found in the skin of poison frogs from the family Dendrobatidae, notably '' Oophaga histrionica'' (formerly ''Dendrobates histrionicus''), which are native to Colombia. It is likely that, as with ot ...
s. This alkaloid skin secretion was first isolated from the tropical frog in 1977 by Daly and his fellow workers.
Biological uses
This compound is a relatively non-toxic chemical. At first it showed activity as a slight
muscarinic
A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.Kishi and his co-workers, here they prepped an intermediate from L-
pyroglutamic acid
Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but understudied natural amino acid derivative in which the free amino group of glutamic acid or glutamine cyclizes to form a lactam. The names of pyroglutamic acid ...
in 18 steps. Others have made it to the same intermediate in fewer steps but have included poorly diastereoselective steps. In 2008 Santarem and colleges reported total synthesis of Gephyrotoxin by obtaining an enantiopure ''cis''-2,5-disubstituted
pyrrolidine
Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most ...
. Unlike others that included a poorly diastereoselective step, this process allowed for the development of two stereogenic centers at the same time.