N-im-Trityl-D-histidine is a protected, non-proteinogenic stereodefined histidine derivative in which the imidazole-containing amino acid side chain is retained while the amino group is protected as an N-im-trityl (trityl) carbocation-stable protecting group. The molecule therefore bears a free carboxyl group and a trityl-protected α-amino functionality, with the histidine imidazole ring providing a basic, hydrogen-bonding side-chain site that can be used for coordination or selective reactivity in peptide and conjugation workflows while the protected amine suppresses undesired amide formation. In synthesis and chemical biology, N-im-Trityl-D-histidine is employed as a stepwise building block for preparing histidine-containing peptides or peptide-related intermediates and for generating labeled or functionalized histidine motifs where controlled protection of the α-amino group supports chemoselective coupling.
CAT No: CP01018
CAS No:199119-46-5
Synonyms/Alias:199119-46-5;H-D-His(Trt)-OH;(R)-2-Amino-3-(1-trityl-1H-imidazol-4-yl)propanoicacid;Nim-Trityl-D-histidine;N-im-Trityl-D-histidine;C25H23N3O2;AC1OLRBK;CTK0H3812;MolPort-020-003-802;D-Histidine,1-(triphenylmethyl)-;ZINC4899667;ANW-43619;AM81826;AJ-52579;AK-49539;RT-014713;ST24035295;V4136;B-7700;J-300147;Q-101824;I14-37398;(2R)-2-amino-3-(1-tritylimidazol-4-yl)propanoicacid
N-im-Trityl-D-histidine is a D-configured histidine derivative in which the imidazole-bearing amino acid framework is N-protected with a trityl group (N-im-Trityl), yielding a chiral amino acid intermediate with a protected α-amino functionality and a free carboxylate or carboxylic acid depending on the supplied form. The imidazole side chain retains its heteroaromatic character and can participate in coordination chemistry, pH-dependent protonation, and selective derivatization strategies after orthogonal deprotection. The bulky trityl protecting group provides steric shielding of the amino terminus, supporting chemoselective peptide coupling workflows where the side-chain imidazole is preserved for later functionalization. The stereochemical integrity of the D-histidine center makes the compound suitable for stereodefined peptide and peptidomimetic construction, as well as for downstream synthetic transformations that rely on controlled amino acid identity.
1. Peptide Synthesis
N-im-Trityl-D-histidine supports peptide building workflows where the N-trityl protection enables controlled amide bond formation at the α-amino position while maintaining the histidine imidazole side chain as a functional handle. The protected amino group can be activated for coupling using standard peptide coupling chemistries, and the orthogonality between N-protection and imidazole reactivity helps manage side reactions during chain assembly. D-stereochemistry is preserved through the intermediate stage, enabling stereodefined incorporation into peptides that require D-histidine residues for conformational tuning and protease resistance studies. The resulting peptide products can then be further processed by imidazole-specific derivatization or selective deprotection steps, aligning the intermediate with protected amino acid synthesis and peptide analog preparation.
2. Side-Chain Functionalization
N-im-Trityl-D-histidine is applicable to side-chain functionalization programs that exploit the histidine imidazole for post-synthetic modification and molecular recognition studies. The free imidazole moiety can be used to introduce metal-binding motifs, affinity tags, or reactive handles through targeted transformations that proceed without requiring α-amino deprotection at the same stage. N-trityl masking of the α-amino group reduces undesired crosslinking or polymerization during side-chain derivatization, supporting cleaner downstream conversion to imidazole-substituted D-histidine derivatives. The ability to generate stereochemically defined, imidazole-functional amino acid building blocks aligns with amino acid derivatization and peptidomimetic construction strategies used in chemical biology research and materials-oriented ligand design.
3. Chemical Biology Probes
N-im-Trityl-D-histidine can be employed in chemical biology probe development where histidine's imidazole enables pH-responsive behavior, metal coordination, and selective binding interactions in biomolecular contexts. The N-protected α-amino group allows preparation of defined amino acid fragments that can be incorporated into peptides, linkers, or scaffolds used for studying protein-ligand interactions and binding-site chemistry. D-histidine incorporation can be used to modulate peptide conformation and stability in probe constructs, supporting structure-activity relationship studies that compare stereochemical variants. The intermediate's protected amino functionality also supports orthogonal conjugation planning, enabling later coupling to biomolecule-reactive groups while retaining the imidazole as the primary interaction motif.
4. Protected Amino Acid Intermediates
N-im-Trityl-D-histidine functions as a protected amino acid intermediate for manufacturing-grade fine chemical synthesis routes that require reliable N-protection and stereodefined amino acid identity. The trityl-protected α-amino group is suited to process designs that separate amino protection management from imidazole-side-chain handling, supporting controlled stepwise synthesis of protected amino acid derivatives and peptide precursors. D-histidine stereochemistry supports the preparation of stereopure intermediates for peptide building block preparation, including downstream conversion to N-deprotected forms and subsequent coupling-ready derivatives. The compound's structural features align with industrial process chemistry intermediate preparation where protection strategy, chemoselectivity, and reproducible intermediate handling are central to scalable peptide and peptidomimetic manufacturing workflows.
5. Analytical Standards And Method Development
N-im-Trityl-D-histidine can serve in analytical research as a stereochemically defined reference material for method development in amino acid analysis, peptide quantification, and protecting-group behavior characterization. The combination of a protected α-amino group and an intact histidine imidazole provides a defined chemical signature that can be used to validate chromatographic separation of protected amino acid species and to monitor deprotection or coupling steps in peptide synthesis workflows. D-configuration offers a discriminating feature for stereospecific assays and for verifying stereochemical integrity in peptide building block preparation. The compound's defined functional group set also supports mass spectrometric and spectroscopic method tuning for detecting protected histidine derivatives in complex synthesis mixtures, aligning with analytical research and quality-by-design practices in applied peptide chemistry.
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