Diethyl L-glutamate hydrochloride
[CAS# 1118-89-4]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Glutamic acid derivative
• Name: Diethyl L-glutamate hydrochloride
• Synonyms: L-Glutamic acid diethyl ester hydrochloride
• Molecular Formula: C₉H₁₇NO₄.HCl
• Molecular Weight: 239.70
• Protein Sequence: X
• CAS Registry Number: 1118-89-4
• EC Number: 214-270-4
• SMILES: CCOC(=O)CC[C@@H](C(=O)OCC)N.Cl

Properties

• Melting point: 108 - 110 °C (Expl.)

Safety Data

• Hazard Symbols: GHS09 Warning
• Risk Statements: H400
• Safety Statements: P273-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovery and Applications

Diethyl L-glutamate hydrochloride is a hydrochloride salt form of diethyl L-glutamate, a derivative of the naturally occurring amino acid L-glutamic acid in which both carboxylic acid groups are esterified with ethyl groups. This compound has drawn interest primarily as a synthetic intermediate and a chemical reagent in pharmaceutical and biochemical research, particularly in studies involving amino acid metabolism, peptide synthesis, and neurobiology.

L-glutamic acid is a key excitatory neurotransmitter in the central nervous system and plays a significant role in neuronal signaling, brain development, and synaptic plasticity. However, the esterified form, diethyl L-glutamate, lacks the ionized acidic groups present in the free acid form, making it more lipophilic and membrane-permeable. This modification allows it to cross lipid membranes more efficiently, including the blood-brain barrier, making it potentially useful for delivering glutamate analogs or related compounds into the brain in research applications.

The hydrochloride salt form improves the stability and solubility of the compound in aqueous systems. As such, diethyl L-glutamate hydrochloride can be employed as a precursor in the synthesis of glutamate-based drugs or analogs where controlled hydrolysis of the ethyl ester groups regenerates the active free acid form intracellularly. This behavior is particularly useful in prodrug strategies, where the ester serves as a temporary protective group, enhancing the compound’s pharmacokinetic properties.

In the field of peptide chemistry, diethyl L-glutamate hydrochloride is also utilized as a building block in the solid-phase or solution-phase synthesis of modified peptides and peptidomimetics. Its esterified form allows for selective reactions at the amino group without interference from the carboxyl functionalities, which are temporarily masked as esters. This selective reactivity is advantageous for introducing glutamate residues into peptide chains in a controlled and efficient manner.

Additionally, diethyl L-glutamate derivatives have been investigated for their role in developing glutamate receptor ligands. The glutamate receptors, including ionotropic receptors such as NMDA and AMPA, and metabotropic glutamate receptors, are targets for various neurological and psychiatric conditions. Modified glutamate analogs based on diethyl L-glutamate scaffolds have been explored for modulating these receptors or serving as diagnostic tools in receptor binding studies.

The compound’s physical and chemical properties, such as its crystalline nature and solubility in polar solvents, make it a practical reagent in both laboratory-scale and larger-scale chemical syntheses. Its relative ease of handling and storage in the hydrochloride form ensures stability under standard laboratory conditions.

While diethyl L-glutamate hydrochloride itself is not typically used as a therapeutic agent, its versatility as a chemical intermediate and probe compound continues to support its use in various research domains, including neurochemistry, drug development, and synthetic organic chemistry.

References

2002. Protease-Catalyzed Regioselective Polymerization and Copolymerization of Glutamic Acid Diethyl Ester. Biomacromolecules, 3(1).
DOI: 10.1021/bm010135c

2008. Synthesis of diethyl N-[p-(methylamino)benzoyl]-L-glutamate. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences, 40(4).
https://pubmed.ncbi.nlm.nih.gov/18677396