Gephyrotoxin
Encyclopedia
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
s. This alkaloid skin secretion was first isolated from the tropical frog in 1977 by Daly and his fellow workers.
, but with recent studies it has showed other interesting neurological activities. Due to these new activities, many laboratories want to conduct future research on it. Due to this demand and the scaracity and unabundance of the tree frog the synthesis of this product is of much interest.
and his co-workers, here they prepped an intermediate from L-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 the obtention of an enantionpure cis-2,5-disubstituted pyrrolidine
. Unlike others that included a poorly diastereoselective step, this process allowed for the development of two stereogenic centers at the same time.
Histrionicotoxin
Histrionicotoxins are a group of related toxins found in the skin of poison frogs from the Dendrobatidae family, notably Dendrobates histrionicus...
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 antagonistReceptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
, but with recent studies it has showed other interesting neurological activities. Due to these new activities, many laboratories want to conduct future research on it. Due to this demand and the scaracity and unabundance of the tree frog the synthesis of this product is of much interest.
Synthesis
The first total synthesis of gephyrotoxin was performed by KishiYoshito Kishi
Yoshito Kishi is the Morris Loeb Professor of Chemistry at Harvard University. He is known for his contributions to the sciences of organic synthesis and total synthesis....
and his co-workers, here they prepped an intermediate from L-pyroglutamic acid
Pyroglutamic acid
Pyroglutamic acid is an uncommon amino acid derivative in which the free amino group of glutamic acid cyclizes to form a lactam. It is found in many proteins including bacteriorhodopsin. N-terminal glutamine residues can spontaneously cyclize to become pyroglutamate...
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 the obtention of an enantionpure cis-2,5-disubstituted pyrrolidine
Pyrrolidine
Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula C4H9N. It is a cyclic secondary amine with a five-membered heterocycle containing four carbon atoms and one nitrogen atom...
. Unlike others that included a poorly diastereoselective step, this process allowed for the development of two stereogenic centers at the same time.