Fmoc-2,5-Difluoro-D-Phenylalanine is an Fmoc-protected, non-natural amino acid derivative in which the phenylalanine side chain bears two fluorine atoms at the 2- and 5-positions relative to the benzylic carbon. The molecule contains a free carboxyl group and an amino group masked as an Fmoc carbamate, while the D stereochemical configuration is specified by the product name and the difluorinated aromatic ring provides altered electronic and steric characteristics compared with unsubstituted phenylalanine. In peptide chemistry and chemical biology workflows, this protected amino acid is used as a building block to introduce a difluorinated, stereodefined aromatic residue during stepwise peptide synthesis and to support structure-activity studies, labeling strategies, or analytical investigations of fluorinated peptide analogues.
CAT No: CP12807
Fmoc-2,5-Difluoro-D-Phenylalanine is an N-(9H-fluoren-9-ylmethoxycarbonyl) protected, chiral amino acid derivative in which the D-configuration is retained at the α-carbon and two fluorine atoms are installed on the phenyl ring at the 2- and 5-positions. The structure combines an Fmoc-protected primary amine with a carboxylic acid functionality, enabling controlled peptide coupling after standard deprotection and activation. The aromatic ring bearing geminally separated aryl fluorides increases electron-withdrawing character and can modulate conformational preferences and metabolic stability in downstream peptide and peptidomimetic analogs. The presence of orthogonal functional handles, including the Fmoc carbamate and the carboxylic acid, supports compatibility with solid-phase peptide synthesis and solution-phase derivatization workflows that require stereodefined, fluorinated amino acid building blocks.
1. Peptide Synthesis
Fmoc-2,5-Difluoro-D-Phenylalanine is used in peptide building block preparation for solid-phase and solution-phase peptide synthesis where Fmoc deprotection reveals a protected amine suitable for amide bond formation. The D-phenylalanine stereocenter provides stereochemical control during coupling, while the carboxylic acid enables activation strategies compatible with common peptide coupling chemistries. The 2,5-difluoro-substituted aryl side chain can be incorporated to tune hydrophobicity, aromatic electronics, and potential fluorine-mediated interactions in peptide sequences. Incorporation into peptide chains supports the generation of fluorinated analog libraries for structure-activity relationship studies and for producing peptide standards used in analytical method development.
2. Peptidomimetics And SAR
Fmoc-2,5-Difluoro-D-Phenylalanine is applied in peptidomimetic construction and SAR studies where the fluorinated phenyl ring functions as a chemically stable aromatic motif for scaffold diversification. The aryl fluorines at the 2- and 5-positions provide distinct electronic effects and can influence binding site recognition through altered polarizability and specific halogen-related contacts. The D-configuration at the α-carbon supports incorporation of conformationally biased or protease-resistant peptide analogs, which can be useful for mapping sequence determinants in biochemical assays. Downstream peptide analog formation can leverage the Fmoc handle for stepwise assembly, enabling systematic comparison of side-chain electronics and stereochemical effects across related series.
3. Side-Chain Functionalization
Fmoc-2,5-Difluoro-D-Phenylalanine supports amino acid modification strategies that exploit fluorinated aromatic reactivity and protected-group chemistry for controlled downstream transformations. The Fmoc-protected amine and carboxylic acid allow orthogonal manipulation: Fmoc removal can expose the nucleophilic amine for further conjugation or for incorporation into longer constructs before side-chain derivatization steps. The difluoro-substituted phenyl ring can serve as a handle for subsequent functional group installation via aromatic substitution or cross-coupling approaches in synthetic organic chemistry, depending on the chosen substitution pattern and leaving-group strategy. Resulting fluorinated derivatives can be used to generate chemical probes, intermediate fragments for medicinal chemistry, and materials-oriented aromatic building blocks where halogenated aromatic electronics are desired.
4. Drug Discovery Chemistry
Fmoc-2,5-Difluoro-D-Phenylalanine is utilized in drug discovery chemistry as a chiral, fluorinated amino acid intermediate for producing peptidomimetic and constrained ligand frameworks. The combination of a stereodefined D-α-center and an Fmoc-protected amine supports incorporation into peptide-like scaffolds that can be screened as fragments or as lead-optimization analogs. The 2,5-difluoro phenyl side chain can be used to modulate physicochemical properties such as lipophilicity and aromatic electronic density, which are often correlated with binding behavior and off-target interactions during lead refinement. Subsequent derivatization from the carboxyl group enables formation of activated intermediates for coupling to other heterocycles or for generating SAR-focused libraries of fluorinated analogs.
5. Pharmaceutical Intermediate Preparation
Fmoc-2,5-Difluoro-D-Phenylalanine is suitable for pharmaceutical intermediate preparation in fine chemical manufacturing contexts where stereochemically defined, protected amino acid building blocks are required for reproducible downstream synthesis. The Fmoc carbamate provides a robust protecting group that can be removed under standard deprotection conditions, while the carboxylic acid functionality supports conversion to activated esters or coupling-ready forms during process chemistry. The fluorinated aromatic side chain can be carried through manufacturing routes with controlled handling of functional group reactivity, enabling consistent incorporation into peptide-derived intermediates and reference materials. Downstream utility includes generation of fluorinated peptide fragments and peptidomimetic precursors that feed into broader manufacturing workflows for research-grade and process-development scale syntheses.
6. Analytical Research Standards
Fmoc-2,5-Difluoro-D-Phenylalanine is applied in analytical research for preparing fluorinated amino acid and peptide standards used in method development and impurity profiling. The defined D-stereochemistry and the presence of two aryl fluorines provide strong structural specificity that can aid chromatographic separation and mass spectrometric identification of related species. The Fmoc-protected amine and carboxylic acid allow controlled conversion into peptide conjugates or reference fragments, improving traceability of synthetic intermediates during characterization. Resulting labeled or assembled fluorinated standards can support quantitative and qualitative analyses of peptide coupling outcomes, stereochemical integrity, and side-chain incorporation in amino acid derivative synthesis workflows.
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