4124-76-9

Usage

InChI:InChI=1/C13H13NO5/c15-11-7-6-10(12(16)19-11)14-13(17)18-8-9-4-2-1-3-5-9/h1-5,10H,6-8H2,(H,14,17)

Upstream product

• 1155-62-0 N-benzyloxycarbonyl-L-glutamic acid 
• 56-86-0 L-glutamic acid 
• 501-53-1 benzyl chloroformate 
• 100-51-6 benzyl alcohol 

Downstream Products

• 6384-08-3 L-glutamic acid 1-methyl ester 
• 1499-55-4 L-glutamic acid 5-methyl ester 
• 5672-83-3 Z-L-GluOMe 
• 125511-29-7 L-glutamic acid-1-propyl ester 
• 7391-22-2 L-glutamic acid-5-propyl ester 
• 1119-33-1 (S)-2-Amino-pentanedioic acid 5-ethyl ester 
• 52454-78-1 L-glutamic acid α-ethyl ester 
• 5672-81-1 (4S)-4-{[(benzyloxy)carbonyl]amino}-5-ethoxy-5-oxopentanoic acid 
• 85701-70-8 Z-Glu-Leu-NH₂ 
• 106302-42-5 N-(N-benzyloxycarbonyl-α-L-glutamyl)-L-methionine methyl ester 
• 129601-68-9 N-(N-benzyloxycarbonyl-α-L-glutamyl)-L-glutamic acid diethyl ester 
• 101982-64-3 N-(N-benzyloxycarbonyl-L-α-glutamyl)-L-tyrosine ethyl ester 
• 102111-64-8 N-(N-benzyloxycarbonyl-α-L-glutamyl)-L-phenylalanine ethyl ester 
• 95253-83-1 3.5-diiodo-N-(N-benzyloxycarbonyl-α-L-glutamyl)-L-tyrosine 

Relevant academic research and scientific papers

Solution-phase synthesis of the fluorogenic TGase 2 acyl donor Z-Glu(HMC)-Gly-OH and its use for inhibitor and amine substrate characterisation

A reliable solution-phase synthesis of the water-soluble dipeptidic fluorogenic transglutaminase substrate Z-Glu(HMC)-Gly-OH is presented. The route started from Z-Glu-OH, which was converted into the corresponding cyclic anhydride. This building block was transformed into the regioisomeric α- and γ-dipeptides. The key step was the esterification of Z-Glu-Gly-OtBu with 4-methylumbelliferone. The final substrate compound was obtained in an acceptable yield and excellent purity without the need of purification by RP-HPLC. The advantage of this acyl donor substrate for the kinetic characterisation of inhibitors and amine-type acyl acceptor substrates is demonstrated by evaluating commercially available or literature-known irreversible inhibitors and the biogenic amines serotonin, histamine and dopamine, respectively.

Synthesis of fully protected (2R,3R,4S)-4-amino-7-guanidino-2,3-dihydroxy heptanoic acid

(2R,3R,4S)-4-Amino-7-guanidino-2,3-dihydroxyheptanoic acid (AGDHE), a common constituent of biologically active marine peptides, callipeltin A (1) and neamphamide A, was synthesized as its orthogonally protected derivative from L-glutamic acid in 15 steps. Guanidination by the Mitsunobu condition and osmium-catalyzed dihydroxylation of the corresponding Z-olefin were employed as the key steps.

Structure-CaSR-activity relation of kokumi γ-glutamyl peptides

Modulation of the calcium sensing receptor (CaSR) is one of the physiological activities of γ-glutamyl peptides such as glutathione (γ-glutamylcysteinylglycine). γ-Glutamyl peptides also possess a flavoring effect, i.e., sensory activity of kokumi substances, which modifies the five basic tastes when added to food. These activities have been shown to be positively correlated, suggesting that kokumi γ-glutamyl peptides are perceived through CaSRs in humans. Our research is based on the hypothesis that the discovery of highly active CaSR agonist peptides will lead to the creation of practical kokumi peptides. Through continuous study of the structure-CaSR-activity relation of a large number of γ-glutamyl peptides, we have determined that the structural requirements for intense CaSR activity of γ-glutamyl peptides are as follows: existence of an N-terminal γ-L-glutamyl residue; existence of a moderately sized, aliphatic, neutral substituent at the second residue in an L-configuration; and existence of a C-terminal carboxylic acid, preferably with the existence of glycine as the third constituent. By the sensory analysis of γ-glutamyl peptides selected by screening using the CaSR activity assay, γ-glutamylvalylglycine was found to be a potent kokumi peptide. Furthermore, norvaline-containing γ-glutamyl peptides, i.e., γ-glutamylnorvalylglycine and γ-glutamylnorvaline, possessed excellent sensory activity of kokumi substances. A novel, practical industrial synthesis of regiospecific γ-glutamyl peptides is also required for their commercialization, which was achieved through the ring opening reaction of N-α-carbobenzoxy-L-glutamic anhydride and amino acids or peptides in the presence of N-hydroxysuccinimide.

Synthesis and relaxometric characterization of a MRI Gd-based probe responsive to glutamic acid decarboxylase enzymatic activity

Novel contrast agent based systems, which selectively visualize specific cells, e.g., neurons in the brain, would be of substantial importance for the fast developing field of molecular magnetic resonance imaging (MRI). We report here the synthesis and in vitro validation of a Gd(III)-based contrast agent designed to act as an MRI responsive probe for imaging the activity of the enzyme glutamic acid decarboxylase (GAD) present in neurons. Upon the action of the enzyme, the Gd(III) complex increases its hydration sphere and takes on a residual positive charge that promotes its binding to endogenous macromolecules. Both effects contribute in a synergic way to generate a marked relaxation enhancement, which directly reports enzyme activity and will allow activity detection of GAD positive cells in vitro and in vivo selectively.

Synthesis and Siderophore Activity of Albomycin-like Peptides Derived from N5-Acetyl-N5-hydroxy-L-ornithine

N5-Acetyl-N5-hydroxy-L-ornithine (1), the key constituent of several microbial siderophores, has been synthesized in 23percent yield overall from N-Cbz-L-glutamic acid 1-tert-butyl ester (6) derived from L-glutamic acid.Reduction of 6 to 7 and treatment with N-(trichloroethoxy)carbonyl>-O-benzylhydroxylamine (8), and diethyl azodicarboxylate and triphenylphosphine followed by deprotection produced the protected N5-acetyl-N5-hydroxy-L-ornithine derivatives 11 and 12 in large quantities (10-20 g).Following α-amino and α-carboxyl deprotections of 11 and 12, EEDQ mediated peptide coupling and final deprotection provided amino acid 1 and six albomycin-like peptides (20, 23, 25, 28, 35, and 36).The growth-promoting ability of each was evaluated with the siderophore biosynthesis mutant Shigella flexneri SA240 (SA 100 iucD:Tn5).These results indicate that substantial modification of the framework of peptide-based siderophores can be tolerated by microbial iron-transport systems.

Syntheses of Polypeptides by Hidrogenolysis of N-Benzyloxycarbonyl-Amino Acid Anhydrides

When anhydrides of N-benzyloxycarbonyl-DL-aspartic acid (Z-DL-Asp), Z-L-Asp, N-Z-DL-glutamic acid (Z-DL-Glu), Z-L-Glu and N-Z-3-aminoglutaric acid (Z-β-Agl) were hydrogenolyzed in N,N-dimethylformamide (DMF), polypeptides were obtained in high yields.Hydrogenolyses of Z-DL-Glu and Z-L-Glu in dioxane gave pyroglutamic acid.

Synthesis of a Novel Class of Peptides: Dilactam-Bridged Tetrapeptides

As model compounds for the study of constrained peptides, the following lactam-bridged derivatives were synthesized: Ac-L--D--NHMe (I), Ac-L--L--NHMe (II), Ac-L--NHMe (III), Ac-L--D--NHMe (IV), Ac-L--L--NHMe (V), and Ac-L--NHMe (VI).Benzyloxycarbonyl and tert-butyloxycarbonyl groups were employed for amine protection and the benzyl and methyl esters for carboxyl protection.Coupling reactions were carried out by the use of active esters or through azide activation.Cyclization reactions were carried out by adding the active ester hydrochlorides into large volumes of pyridine at elevated temperatures.The cyclic intermediates were obtained in yields of 45-50percent.Fragment condensation of the cyclic dipeptides yielded the corresponding dilactam-bridged tetrapeptides.

Synthesis of the Dolastatin Thiazole Amino Acid Component (gln)Thz

The new thiazole amino acid (gln)Thz, found to occur as one unit of the marine sea hare cyclic pentapeptide dolastin 3, has been synthesized from L-glutamic acid by the route 2 -> 10e.The synthesis of Z-L-isoglutamine (4) was improved by selective ammonolysis of anhydride 3 at -60 deg C.A variety of reaction conditions were found to cause complete racemization during the Hantzsch thiazole synthesis step (9 -> 10).Deuterium labeling experiments indicated loss of the chiral center prior to formation of the thiazole system and suggested an imine-enamine type equilibration involving intermediates A B (Scheme II).The N-benzyloxycarbonyl derivative (10d) of (gln)Thz was partially resolved by employing brucine.