Glutamic acid analogs

Cyclization reactions of glutamic acid analogous to those of aspartic acid have not been found in sequence studies with peptides, but an a — 7 interconversion in model peptides of glutamic acid has been observed (Kornguth el al., 1963). 

Chemical Abstracts Service Registry Number CAS 14277-97-5. Domoic acid, a glutamic acid analog that is resistant to temperature extremes, is an excitatory neurotoxin produced by a diatom and concentrated in shellfish. Ingestion leads to amnesic shellfish poisoning, which can also include seizures. Its relevance to use in warfare and terrorism, apart from its being unfamiliar to most disaster-response personnel, is that it is also easily absorbed by inhalation and across mucous membranes. No specific antitoxin is available, and treatment is supportive. 

Winter HC, Ueda T (1993) Glutamate uptake system in the presynaptic vesicle glutamic acid analogs as inhibitors and alternate substrates. Neurochem Res 78 79-85. 

D. S. Radchenko, O. O. Grygorenko, I. V. Komarov, Tetrahedron Asymmetry 2008, 19, 2924—2930. Synthesis of conformationally restricted glutamic acid analogs based on the spiro[3.3]heptane scaffold. 

The conformationally restricted glutamic acid analog LY404039 (1) was recently found to be a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors and has shown antipsychotic potential in animal studies. In order to fuel further development, a scalable and robust synthetic route for the 8-step synthesis of 1 from thiophene was developed and successfully implemented on 60-70 kg pilot-plant scale. 

Another type of phase-transfer catalyst based on binaphtyl quaternary ammonium salt such as 194 could be used in the creation of amino acid bearing a tetra-substituted stereocenter.Up to 97% ee could be obtained for the generation of glutamic acid analog 196, an excitatory neurotransmitter. 

The 20 ammo acids listed m Table 27 1 are biosynthesized by a number of different path ways and we will touch on only a few of them m an introductory way We will exam me the biosynthesis of glutamic acid first because it illustrates a biochemical process analogous to a reaction we discussed earlier m the context of amine synthesis reductive ammatwn (Section 22 10)... 

Several quinoxaline analogs of pteroic acid (114) and pteroyl-glutamic acid (115) have been prepared. " - Quinoxaline-2-aldehyde,... 

The glutamic moiety of TNP-351, a pyrrolo[2,3-d]pyrimidine glutamic acid derivative, and related compounds have been transformed into their A-co-masked ornithine analogs which show remarkable antifolate activity <00CPB1270>. The reaction of the heterocyclic enamine 77 with tosyl azide leads to the tosylimino derivative of 1,2,4-triazolo[l, 5-a]pyrimidine 79. Extrusion of nitrogen from the primary adduct 78 is followed by a 1,2-shift of a methyl group to yield 79 <00JHC195>. 

Oleksyszyn, J., Gruszecka, E., Kafarski, P., and Mastalerz, P., New phosphonic analogs of aspartic and glutamic acid by aminoalkylation of trivalent phosphorus chlorides with ethyl acetoacetate, ethyl levulinate and benzyl carbamate, Monatsh. Chem., 113, 59, 1982. 

A substituted acetamidomalonic ester, tetraethyl 1 -acetamido-4-hydroxy-butane-l,l,3,3-tetracarboxylate, was used in the preparation of cis- and frans-pyrrolidine-2,4-dicarboxylic acids, cyclic analogs of glutamic acid (91TL3049). 

In the transamination reaction, in the presence of transaminase enzymes, (S)-glutamic acid reacts with the a-keto acid analog of the desired a-amino acid to give the desired (S)-amino acid and the keto analog of glutamic acid. 

L-Cycloserine inhibits many PLP enzymes and is toxic to humans. This observation led Khomutov et al. to synthesize the following more specific "cycloglutamates," structural analogs of glutamic acid with fixed conformations J/k Nature apparently anticipated the synthetic chemist, because it has been reported that the mushroom Tricholoma muscar-... 

---