H-alpha-Me-DL-His-OH · 2 HCl is a free, amino acid derivative of histidine bearing an alpha-methyl substituent (α-Me) and existing as a DL (racemic) mixture, with the imidazole side chain characteristic of the histidine family. The molecule contains an amino group and a carboxylic acid, while the imidazole ring provides basic functionality and the α-methyl substitution alters steric and conformational properties relative to unmodified histidine; the "· 2 HCl" indicates formation of a dihydrochloride salt that accompanies protonation of basic sites. In peptide and amino acid chemistry workflows, this salt form is used as a defined, structurally modified histidine analogue for incorporation into synthetic sequences and for structure-activity or labeling studies where α-methyl substitution and racemic stereochemical composition are relevant to binding or analytical behavior.
CAT No: CP26997
CAS No:32381-18-3
Synonyms/Alias:32381-18-3;alpha-Methyl-DL-histidinedihydrochloride;alpha-METHYL-DL-HISTIDINE;SCHEMBL2808246;CTK4G8608;AM022285;Histidine,a-methyl-,dihydrochloride(9CI);ALPHA-METHYL-DL-HISTIDINEDIHYDROCHLORIDE;2-amino-3-(1H-imidazol-4-yl)-2-methylpropanoicaciddihydrochloride;2-AMINO-3-(3H-IMIDAZOL-4-YL)-2-METHYLPROPANOICACIDDIHYDROCHLORIDE
H-alpha-Me-DL-His-OH · 2 HCl is a hydrochloride salt of a DL mixture of an alpha-methylated histidine derivative, featuring an imidazole side chain characteristic of histidine chemistry and an alpha stereocenter that is present as a racemic blend. The amino acid framework contains a primary amino group and a carboxylic acid functionality, both present under salt conditions as indicated by the two equivalents of HCl, which can influence solubility and handling during peptide coupling and derivatization. The alpha-methyl substitution modulates conformational preferences and steric environment around the backbone, while the imidazole can participate in protonation-state dependent reactivity and coordination chemistry. As a chiral amino acid intermediate precursor to substituted histidine motifs, the compound can be incorporated into protected amino acid synthesis workflows and downstream peptide or peptidomimetic construction using standard amino acid coupling strategies.
1. Peptide Synthesis
H-alpha-Me-DL-His-OH · 2 HCl is applied in peptide building-block preparation where an alpha-methylated histidine residue is required to probe backbone sterics and imidazole-bearing side-chain behavior. The imidazole side chain and the amino acid backbone enable conversion into N-protected and, when needed, C-activated forms suitable for peptide coupling, while the alpha-methyl group can steer local conformations and affect coupling efficiency and amide bond formation kinetics. Salt formation with HCl supports consistent handling during protection steps and can improve aqueous compatibility for intermediate transformations. Resulting peptide analogs can be used to generate histidine-containing sequences for mechanistic studies and peptide library construction.
2. Peptidomimetics
H-alpha-Me-DL-His-OH · 2 HCl serves as a chiral amino acid intermediate for peptidomimetic scaffold design targeting enhanced resistance to proteolysis and altered side-chain presentation. The alpha-methyl substitution provides a stereochemically defined backbone element that can be leveraged to create constrained amide linkages or to build non-natural histidine-containing analogs with tuned conformational profiles. The imidazole functional group can be retained for metal coordination studies or chemically modified for controlled hydrogen-bonding and receptor interaction mapping. Downstream derivatives may include cyclized or backbone-modified structures that remain compatible with fragment-based molecular design and medicinal chemistry optimization.
3. Chemical Biology
H-alpha-Me-DL-His-OH · 2 HCl is used in chemical biology research to generate histidine-based probes and affinity handles that exploit imidazole protonation and metal-binding characteristics. The amino acid salt form can be converted into protected derivatives for incorporation into peptides, linkers, or labeling reagents, enabling controlled placement of the imidazole group within a biomolecular context. Alpha-methylation can influence local backbone geometry, which may affect binding orientation, accessibility, and labeling stoichiometry in conjugation workflows. The resulting amino acid derivatives and peptide conjugates can be employed for studying protein-ligand interactions, binding site microenvironments, and coordination-driven recognition.
4. Protected Amino Acids
H-alpha-Me-DL-His-OH · 2 HCl functions as a starting material for protected amino acid synthesis where orthogonal protection strategies are required for selective peptide coupling. The presence of both an amino group and a carboxylic acid allows conversion into N-protected amino acid derivatives and, when desired, ester or activated carboxyl derivatives, while the imidazole may be protected or left unprotected depending on coupling conditions and downstream selectivity. The alpha-methyl stereocenter, even as a DL mixture, provides a defined steric motif that persists through protection and activation steps, supporting consistent incorporation into peptide building blocks. Protected intermediates derived from this compound can be used for iterative peptide assembly, automated synthesis compatibility, and scalable fine chemical production of substituted histidine residues.
5. Process Chemistry
H-alpha-Me-DL-His-OH · 2 HCl is relevant to process chemistry intermediate preparation for manufacturing substituted amino acid derivatives with robust salt handling and defined functional-group reactivity. The hydrochloride salt form supports predictable acid-base behavior during protection, activation, and purification operations, which can be advantageous when designing reproducible routes for amino acid ester synthesis and peptide coupling precursor generation. The alpha-methylated backbone can be maintained throughout multi-step sequences, enabling downstream formation of activated carboxylic acid derivatives and N-protected intermediates used in peptide manufacturing. Industrially oriented workflows can apply this compound as a feedstock to produce histidine-containing intermediates for specialty chemical production and peptide building-block supply chains.
6. Analytical Standards
H-alpha-Me-DL-His-OH · 2 HCl is suitable for analytical research and method development where alpha-methylated histidine standards are needed to validate amino acid derivatization, imidazole-containing metabolite profiling, or peptide hydrolysate analysis. The imidazole side chain and the alpha-methylated backbone provide a distinct mass and chromatographic signature relative to native histidine, supporting targeted detection in LC-MS and related analytical platforms. Salt form can improve reproducibility in sample preparation and can be used to generate reference materials for calibration of derivatization workflows. Analytical-grade derivatives prepared from this compound can also serve as internal standards for monitoring amino acid ester synthesis, protection-state transformations, and peptide coupling precursor integrity.
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