Synthesis and characterization of N,N-dichlorinated amino acids: taurine, homotaurine, GABA and L-leucine.
Epilepsy, trauma and other circumstances leading to hyperexcitable conditions in the CNS tend neurochemically to be associated with excessive stimulated release of glutamic acid and/or a failure of GABA modulated inhibition. Somewhat to a lesser extent, taurine and its homologue homotaurine, have also been shown to antagonize the excitatory actions of glutamic acid. Here we report the successful synthesis and isolation in pure form of N,N-dichlorinated GABA, taurine, homotaurine and leucine. These compounds are much more lipophilic than their parent compounds and may therefore more readily penetrate the blood-brain barrier systems into the neural tissue, where they can be easily dechlorinated. Very preliminary biological testing shows that this may indeed occur. The synthesis and purification methodology will likely also be applicable to a number of other amino acids as well as certain peptides or selected proteins.
van Gelder
N M
NM
Deparment of Chemistry, Queen's University, Kingston, Ontario. Canada. vangeldr@chem.queensu.ca
Bowers
R J
RJ
D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013654:Taurine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D013654:Taurine; D005680:gamma-Aminobutyric Acid; C001355:tramiprosate; D007930:Leucine