Fmoc-2,3-Difluoro-D-Phenylalanine is an Fmoc-protected, non-natural phenylalanine derivative bearing two fluorine atoms at the 2- and 3-positions of the amino acid backbone and a D-configuration at the stereogenic center indicated by the product name. The molecule contains a free carboxyl group and an Fmoc (9H-fluoren-9-ylmethoxycarbonyl) carbamate on the amino functionality, while the difluorinated side-chain region alters steric and electronic character relative to unmodified phenylalanine. It is used as a protected amino acid building block for peptide synthesis and structure-activity studies where incorporation of a fluorinated aromatic residue supports chemical probing, conformational effects, and analytical method development.
CAT No: CP12607
Fmoc-2,3-Difluoro-D-Phenylalanine is an Fmoc-protected D-phenylalanine derivative bearing two fluorine atoms at the 2- and 3-positions of the amino acid backbone. The molecule combines a chiral α-carbon stereocenter with a stereochemically defined difluorinated side of the backbone, while the aromatic phenyl ring provides a hydrophobic handle for peptide and peptidomimetic recognition. The Fmoc group masks the amino functionality for controlled peptide coupling, whereas the geminal and vicinal fluorine substitution pattern strongly modulates acidity, sterics, and conformational preferences of the resulting amide linkage. The difluoro motif can participate in downstream derivatization and can tune physicochemical properties of peptides and small molecules, making this chiral amino acid intermediate suitable for structure-guided synthetic chemistry and analytical method development.
1. Peptide Synthesis
Fmoc-2,3-Difluoro-D-Phenylalanine is used in peptide building workflows where Fmoc removal and subsequent amide bond formation are required to incorporate a stereodefined difluorinated residue. The protected amine enables standard peptide coupling chemistry, while the D-configuration at the α-position supports stereochemical control in growing peptide chains. The 2,3-difluoro substitution adjacent to the carbonyl can influence backbone conformations and local hydrogen-bonding patterns, which is relevant when constructing peptides for SAR studies or conformational probing. The resulting difluorinated peptide analogs can serve as downstream intermediates for further functionalization, including side-chain or terminal modifications that preserve the fluorinated stereocenter.
2. Peptidomimetics And SAR Studies
Fmoc-2,3-Difluoro-D-Phenylalanine is applied in peptidomimetic design to introduce a fluorinated phenylalanine analog that can alter lipophilicity, metabolic stability, and conformational bias of peptide-like scaffolds. The difluoro substitution at the backbone positions adjacent to the amide can affect torsional preferences and can modulate interactions with binding pockets through altered dipole character and steric profile. The D-configuration provides a stereochemically distinct variant relative to L analogs, enabling structure-activity relationship studies that compare stereochemical and electronic effects. Incorporation into short peptide fragments or larger mimetics supports generation of fluorinated analog series for medicinal chemistry and biochemical binding characterization.
3. Chemical Biology Labeling
Fmoc-2,3-Difluoro-D-Phenylalanine is suitable for chemical biology research where fluorinated amino acid residues are incorporated to create tracers or probes with altered physicochemical behavior compared with non-fluorinated counterparts. The Fmoc-protected amino acid format supports incorporation into peptide conjugates or protein-reactive constructs through controlled deprotection and coupling steps. The difluoro backbone can provide a chemically distinct motif for analytical differentiation by fluorine-sensitive detection methods and for mass-based identification of labeled biomolecules. Downstream conjugate preparation can leverage the fluorinated residue as a stable structural element within larger biomolecule labeling strategies, including affinity probes and imaging-relevant molecular tags.
4. Chiral Building Block Development
Fmoc-2,3-Difluoro-D-Phenylalanine is employed as a chiral amino acid intermediate for stereoselective synthesis of fluorinated fragments used in medicinal chemistry and specialty chemical production. The D-stereocenter and the fixed 2,3-difluoro substitution pattern create a defined three-dimensional motif that can be carried through to amide-containing intermediates and final scaffolds. The Fmoc protecting group enables orthogonal handling of the amino functionality during multi-step synthesis, supporting stepwise assembly of complex molecules without premature side reactions. The resulting difluorinated products can serve as key intermediates for fine chemical synthesis, including preparation of fluorinated peptide analogs, chiral amide derivatives, and other stereochemically defined building blocks.
5. Pharmaceutical Manufacturing Intermediates
Fmoc-2,3-Difluoro-D-Phenylalanine is relevant to pharmaceutical manufacturing workflows that require reproducible incorporation of protected, stereodefined amino acid residues into peptide-based intermediates. The Fmoc-protected amine supports controlled deprotection and coupling logic consistent with solid-phase or solution-phase peptide synthesis strategies used to generate drug-like peptidic materials. The difluoro backbone can be used to tune properties of peptide intermediates, which may influence downstream purification behavior, stability of intermediates, and robustness of analytical characterization. The compound's defined stereochemistry and protected functional group profile make it suitable as a process chemistry intermediate for producing fluorinated peptide analogs and related manufacturing feedstocks.
6. Analytical Research Standards
Fmoc-2,3-Difluoro-D-Phenylalanine is used for analytical research where fluorinated amino acid standards help validate identification and quantification of difluoro-containing peptides and hydrolysis products. The presence of two fluorine atoms and the D-configuration provides a distinctive signature that can support method development using mass spectrometry and fluorine-sensitive detection approaches. The Fmoc-protected form supports preparation of defined peptide derivatives that can be used as reference materials for chromatographic behavior and fragmentation pattern assignment. Downstream, the compound can serve as a biochemical research intermediate for generating calibration sets and structural controls that improve the reliability of analytical workflows targeting fluorinated amino acid incorporation.
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