3,4-Difluoro-L-Phenylalanine is a fluorinated, proteinogenic amino acid analogue in which the phenylalanine side chain bears two fluorine substituents at the 3- and 4-positions relative to the benzylic carbon, retaining the L-configuration at the alpha stereocenter. The molecule contains a free alpha-amino group and a free carboxyl group and features an aromatic benzyl side chain whose electron-withdrawing fluorines modulate polarity, hydrogen-bonding patterns, and aromatic interactions compared with unsubstituted phenylalanine. It is used in peptide and protein engineering and structure-function studies where incorporation of a difluorinated aromatic residue supports chemical biology experiments, labeling strategies, and analytical method development that distinguish fluorinated amino acid-containing constructs.
CAT No: CP13001
CAS No:31105-90-5
Synonyms/Alias:31105-90-5;3,4-difluoro-l-phenylalanine;L-3,4-Difluorophenylalanine;(S)-2-Amino-3-(3,4-difluorophenyl)propanoicacid;(2S)-2-amino-3-(3,4-difluorophenyl)propanoicacid;L-3,4-DIFLUOROPHE;AC1LEQCL;PubChem17977;AC1Q4NVP;SCHEMBL44052;H-D-Phe(3,4-DiF)-OH;H-PHE(3,4-DIF)-OH;L-PHE(3,4-DIF)-OH;CTK8C4800;H-PHE(3,4-F2)-OH;MolPort-001-777-558;ZINC113751;H-3,4-DIFLUORO-L-PHE-OH;H-L-PHE(3,4-F2)-OH;ANW-73158;AR-1E9148;CD-724;AKOS015854042;AB08129;AL176-1
3,4-Difluoro-L-Phenylalanine is a fluorinated L-phenylalanine analog featuring two fluorine atoms on the aromatic ring, providing a chemically distinctive side-chain electronics profile while retaining the standard amino acid backbone for peptide incorporation and medicinal chemistry derivatization. Researchers use this non-natural amino acid building block to introduce aryl fluorination patterns that can influence conformational preferences, metabolic stability trends, and binding interactions in structure-activity relationship (SAR) studies. Its defined stereochemistry and aromatic functionality make it a practical reagent for preparing fluorinated peptides and for generating fluorinated intermediates used in drug discovery chemistry.
1. Fluorinated Peptide Building Block
3,4-Difluoro-L-Phenylalanine is used as an amino acid building block for custom peptide synthesis where incorporation of a difluorinated phenylalanine residue is required for SAR mapping, structure-activity optimization, or mechanistic peptide studies. Peptide chemists commonly select this residue when they want to systematically vary aromatic substitution while keeping the peptide backbone and side-chain identity comparable to phenylalanine-based designs. The difluoro substitution pattern supports the preparation of fluorinated peptide analogs for downstream characterization such as LC-MS confirmation, MS/MS fragmentation profiling, and comparative stability or binding assays in chemical biology workflows.
2. Medicinal Chemistry SAR Studies
3,4-Difluoro-L-Phenylalanine is widely used in medicinal chemistry programs to access fluorinated aryl motifs that are difficult to obtain from unsubstituted phenylalanine while maintaining a stereochemically defined amino acid handle for stepwise synthesis. Medicinal chemistry teams employ it to generate fluorinated intermediates and analog series for SAR studies, particularly when aromatic fluorination is used to tune physicochemical properties and probe structure-function relationships. The 3,4-difluoro substitution also provides a convenient chemical "tag" for analytical tracking by mass spectrometry, supporting iterative lead optimization and analog comparison in lead discovery and preclinical chemistry research.
3. Protein Engineering Probing
3,4-Difluoro-L-Phenylalanine is used in chemical biology and protein engineering research to introduce a defined difluorinated aromatic side chain into peptide or protein contexts for interaction mapping and residue-level probing. Researchers rely on its L-configuration and amino acid functionality to enable incorporation into designed peptide constructs, facilitating studies that compare how specific aromatic substitution patterns affect local structure, binding footprints, or conformational behavior. In workflows that generate fluorinated protein fragments or engineered peptide domains, the difluoro phenylalanine residue provides a stable, well-defined chemical perturbation that can be tracked and distinguished analytically during characterization.
4. Fluorinated Analytical Standards
3,4-Difluoro-L-Phenylalanine is also used as a reference material and analytical standard precursor for confirming the identity of fluorinated amino acid residues and for supporting method development in LC-MS workflows. Analytical chemists and quality-focused research groups use it when preparing calibration or system suitability materials for assays that monitor fluorinated peptide fragments, hydrolysis products, or difluorinated aromatic motifs. The presence of two fluorine atoms yields a clear mass signature, helping streamline identification and quantitation during analytical method development for fluorinated compound series.
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