D-Tryptophan methyl ester hydrochloride
[CAS# 14907-27-8]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Tryptophan derivatives
• Name: D-Tryptophan methyl ester hydrochloride
• Synonyms: Methyl (2R)-2-amino-3-(1H-indol-3-yl)propanoate hydrochloride; (S)-2-Amino-3-(1H-indol-3-yl)-propionic acid methyl ester hydrochloride
• Molecular Formula: C₁₂H₁₄N₂O₂.HCl
• Molecular Weight: 254.71
• Protein Sequence: W
• CAS Registry Number: 14907-27-8
• EC Number: 639-469-7
• SMILES: COC(=O)[C@@H](CC1=CNC2=CC=CC=C21)N.Cl

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H315-H318-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Serious eye damage	Eye Dam.	1	H318
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

D-Tryptophan methyl ester hydrochloride is the hydrochloride salt form of the methyl ester derivative of D-tryptophan, an essential aromatic amino acid. Chemically, it consists of the D-enantiomer of tryptophan, where the carboxylic acid group is converted into a methyl ester, and the molecule is protonated at the amino group with an associated chloride counterion. This compound appears as a crystalline solid, typically white to off-white in color, and is soluble in polar solvents such as water and alcohols due to its ionic character and ester functionality.

The synthesis of D-tryptophan methyl ester hydrochloride generally involves the esterification of D-tryptophan with methanol under acidic conditions, often using hydrogen chloride gas or hydrochloric acid as a catalyst and to form the hydrochloride salt simultaneously. This reaction converts the free carboxylic acid into the corresponding methyl ester, increasing the compound’s lipophilicity and improving its solubility in organic solvents. The hydrochloride salt formation stabilizes the amine moiety by protonation, enhancing the compound’s crystallinity and shelf-life.

This compound is widely used as an intermediate in peptide synthesis and pharmaceutical research. The methyl ester group serves as a protecting group for the carboxyl function, allowing selective reactions at other sites of the molecule such as the amino group or the indole side chain. Upon completion of synthetic steps, the ester can be hydrolyzed back to the free acid under acidic or basic conditions. The D-configuration is important in studies of stereochemistry, protein interactions, and enzyme specificity, as it differs from the natural L-tryptophan found in proteins.

In medicinal chemistry, D-tryptophan methyl ester hydrochloride is employed in the design and synthesis of peptidomimetics and biologically active peptides. It facilitates the exploration of structure-activity relationships (SAR) by allowing modifications of the amino acid backbone while preserving or altering stereochemical properties. Additionally, it is utilized in the synthesis of analogs that modulate serotonin receptors or serve as precursors for fluorescent probes, given the intrinsic fluorescence of the indole ring.

The compound is also relevant in analytical and preparative chemistry, where it can be used as a reference standard or reagent in chiral chromatography and enantioselective synthesis. Its defined stereochemistry and stable ester form make it suitable for use in automated peptide synthesizers and solid-phase synthesis protocols.

Handling of D-tryptophan methyl ester hydrochloride requires standard laboratory precautions. It should be stored in a cool, dry place protected from moisture and light to prevent hydrolysis of the ester and degradation of the compound. While not highly toxic, care should be taken to avoid inhalation, ingestion, or prolonged skin contact.

In summary, D-tryptophan methyl ester hydrochloride is a crystalline hydrochloride salt of the methyl ester derivative of the D-enantiomer of tryptophan. It is a valuable intermediate in synthetic and medicinal chemistry, particularly in peptide synthesis and stereochemical studies, due to its stability, solubility, and role as a protected amino acid derivative.

References

2021. Structure-activity relationship studies on Pd176252 derivatives leading to discovery of novel GRP receptor antagonist with potent anticancer activity. Medicinal Chemistry Research, 30(9).
DOI: 10.1007/s00044-021-02793-8

2020. High-throughput assay for determining enantiomeric excess of chiral diols, amino alcohols, and amines and for direct asymmetric reaction screening. Nature Protocols, 15(6).
DOI: 10.1038/s41596-020-0329-1

2017. Synthesis and antiviral activity of novel glycyrrhizic acid conjugates with D-amino acid esters. Russian Journal of Bioorganic Chemistry, 43(4).
DOI: 10.1134/s1068162017040045