N-α-Fmoc-N-im-trityl-D-histidine is a protected histidine derivative in which the α-amino group is capped with an Fmoc (9H-fluoren-9-ylmethoxycarbonyl) protecting group and the imidazole nitrogen is substituted with a trityl (trityl/Trt) group, yielding a non-free amino acid suitable for stepwise peptide assembly. The molecule retains the carboxyl functional group and the histidine side chain imidazole ring, but both the α-amino functionality and the imidazole nitrogen are masked to control chemoselectivity and suppress undesired side reactions during coupling and deprotection steps, with the D stereochemical form indicated by the product name. In peptide synthesis workflows, the orthogonally protected architecture supports sequential formation of peptide bonds while providing a protected handle for later unmasking of the histidine imidazole under conditions compatible with the Fmoc and trityl protecting groups, and the compound can be used to prepare histidine-containing peptide intermediates for structure-activity studies or analytical method development.
CAT No: CP01013
CAS No:135610-90-1
Synonyms/Alias:FMOC-D-HIS(TRT)-OH;135610-90-1;N-Fmoc-N'-trityl-D-histidine;PubChem18930;N-Fmoc-1-trityl-D-histidine;Fmoc-N-Im-Trityl-D-histidine;AC1Q719U;SCHEMBL13227674;MolPort-003-983-038;N-|A-Fmoc-N-im-trityl-D-histidine;CF-802;ZINC71788094;AKOS015895738;AKOS015924158;AM81822;AK-49364;SC-09584;FT-0658754;ST24047257;ST51053062;M03417;I06-1410;J-300145;Q-101822;N-[(9H-Fluoren-9-Yl-Methoxy)Carbonyl]-1-Trityl-D-Histidine
N-α-Fmoc-N-im-trityl-D-histidine is an Fmoc-protected D-histidine derivative in which the α-amino group is masked by the fluorenylmethoxycarbonyl (Fmoc) protecting group while the imidazole side chain is protected as an N-im trityl (trityl/Trt) adduct. The molecule retains the histidine backbone stereochemistry at the α-carbon, providing a defined chiral center for stereochemically controlled peptide assembly. The Fmoc carbamate and N-im Trt group modulate nucleophilicity of the amino and imidazole functionalities, respectively, enabling selective deprotection and coupling sequences during protected amino acid synthesis. The presence of an aromatic trityl group and an imidazole ring protected at the N-im position yields a stable, transportable peptide building block that can be converted into histidine-containing peptides and downstream functionalized intermediates through orthogonal protecting-group strategies.
1. Peptide Synthesis
N-α-Fmoc-N-im-trityl-D-histidine is used in peptide building block preparation for solid-phase peptide synthesis and related coupling workflows where orthogonal protection of the histidine side chain is required. The Fmoc-protected α-amino group supports iterative N-terminal deprotection and amide bond formation, while the N-im trityl protection suppresses imidazole participation during coupling and minimizes side reactions. The D-configuration at the α-carbon enables incorporation of D-histidine residues into peptide sequences for stereochemical studies, D-amino acid peptide analog construction, and conformational tuning. The protected histidine motif can be revealed after peptide assembly by selective side-chain deprotection, enabling formation of histidine-reactive peptides for subsequent derivatization or biochemical interrogation.
2. Peptidomimetics And SAR Studies
N-α-Fmoc-N-im-trityl-D-histidine is applied in peptidomimetic construction and structure-activity relationship studies where histidine-like protonation behavior is introduced with controlled stereochemistry. The protected imidazole functionality allows incorporation into peptide-like scaffolds without premature coordination or side-chain reactivity, while the D-amino acid stereocenter supports systematic SAR mapping of stereochemical effects on binding and stability. Fmoc-based handling enables rapid synthesis of analog libraries, and the protected side chain can later be deprotected to restore the imidazole for metal coordination, pH-responsive interactions, or targeted functionalization. The resulting histidine-containing analogs serve as chemical probes and scaffold intermediates for downstream SAR-driven optimization in medicinal chemistry research.
3. Chemical Biology Probes
N-α-Fmoc-N-im-trityl-D-histidine is suitable for chemical biology research requiring controlled installation of histidine residues into peptide probes and labeling handles. The N-im trityl protection provides a means to delay imidazole reactivity during synthesis of probe precursors, supporting compatibility with diverse coupling chemistries and conjugation steps. The restored imidazole after deprotection can participate in selective coordination chemistry, enabling probe designs that rely on imidazole-mediated interactions or pH-dependent behavior. The defined D-histidine stereochemistry can further be used to tune protease resistance and interaction profiles of peptide-based probes used in biochemical assays and molecular recognition studies.
4. Bioconjugation Chemistry
N-α-Fmoc-N-im-trityl-D-histidine is employed in bioconjugation workflows that require protected amino acid incorporation prior to conjugation to biomolecules. The Fmoc-protected α-amino group supports clean peptide fragment assembly, while the trityl-protected imidazole minimizes undesired binding or side reactions during fragment coupling and purification. Deprotection strategies can generate histidine-bearing conjugation-ready intermediates that can then be used to form peptide linkers, attachment motifs, or functional domains in bioconjugates. The chiral D-histidine center provides stereochemical control for linker behavior, which can influence conjugate stability, conformational presentation, and downstream analytical detectability.
5. Process Chemistry Intermediate
N-α-Fmoc-N-im-trityl-D-histidine is relevant to process chemistry intermediate preparation for manufacturing histidine-containing peptide building blocks and protected amino acid derivatives. The orthogonal protecting-group set, combining Fmoc on the α-amino functionality and N-im Trt on the imidazole, supports robust protection during synthesis and predictable deprotection sequences used to design scalable routes. The aromatic protecting groups contribute to crystallinity and handling characteristics that can be leveraged in industrial fine chemical production of protected amino acids for peptide manufacturing. The resulting intermediate can be routed into peptide synthesis supply chains, enabling consistent incorporation of D-histidine residues into higher-value peptide products and research-grade peptide analogs.
6. Analytical Reference Standards
N-α-Fmoc-N-im-trityl-D-histidine is used for analytical research and method development requiring well-defined protected amino acid standards. The presence of both Fmoc and N-im Trt groups provides distinctive mass and fragmentation signatures that can support LC-MS or MS/MS method calibration for protected amino acid intermediates and peptide synthesis monitoring. The defined D-histidine stereochemistry enables stereospecific reference comparisons when analyzing epimerization or protecting-group integrity during peptide building block preparation. Downstream deprotected histidine-containing derivatives generated from this intermediate can also serve as reference materials for validating side-chain functional group transformations and for characterizing peptide products that incorporate D-histidine.
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