Fmoc-2,4-Difluoro-D-Phenylalanine is an Fmoc-protected, non-natural amino acid derivative in which the phenylalanine side chain bears two fluorine substituents at the 2- and 4-positions of the aromatic ring and the alpha center is in the D stereochemical configuration. The molecule contains an Fmoc carbamate protecting group on the amino functionality, while the carboxyl group remains available for coupling as a free acid (or can be converted to a reactive derivative in peptide synthesis), and the difluorinated aryl side chain provides distinct hydrophobic and electronic characteristics relative to unsubstituted phenylalanine. It is used as a building block for incorporating a fluorinated aromatic residue into peptides via stepwise peptide synthesis, supporting structure-activity and chemical biology studies where controlled changes in aromatic electronics and labeling handles are required.
CAT No: CP12707
Fmoc-2,4-Difluoro-D-Phenylalanine is an Fmoc-protected, D-configured phenylalanine derivative in which two fluorine atoms are installed at the 2- and 4-positions of the aromatic ring. The molecule contains a chiral α-carbon bearing the Fmoc-protected amino group and a carboxyl functionality masked for peptide coupling compatibility, while the difluoro-substituted aryl ring modulates electronic density, lipophilicity, and conformational preferences through C-F bond effects. The presence of the Fmoc carbamate enables standard base-labile deprotection under peptide synthesis conditions, and the aryl fluorines provide handles for subsequent derivatization, cross-coupling chemistry, and structure-guided SAR exploration. The combination of stereochemical control from the D-configuration and fluorinated aromatic reactivity makes this compound a chiral amino acid intermediate suited to protected amino acid synthesis and downstream peptide or peptidomimetic construction.
1. Peptide Synthesis
Fmoc-2,4-Difluoro-D-Phenylalanine is applied in solid-phase peptide synthesis and related peptide building workflows where a D-amino acid residue is required for stereochemical control and protease resistance design. The Fmoc-protected amine supports orthogonal coupling strategies after Fmoc removal, while the difluorinated phenyl side chain provides a chemically stable aromatic motif that can influence backbone torsion and local binding environments. The aromatic C-F bonds tolerate common peptide-manufacturing conditions and can be retained through coupling, deprotection, and fragment assembly steps. The resulting fluorinated peptide products can serve as defined chiral analogs for library generation, peptide structure probing, and synthetic methodology development in amino acid chemistry.
2. Peptidomimetics And SAR Studies
Fmoc-2,4-Difluoro-D-Phenylalanine is used in peptidomimetic construction and structure-activity relationship studies where fluorinated aryl electronics are leveraged to tune binding interactions. The D-configuration at the α-carbon introduces stereochemical differentiation relative to L-phenylalanine analogs, enabling systematic evaluation of stereochemical effects on receptor or target recognition in SAR workflows. The 2,4-difluoro substitution pattern can alter hydrogen-bonding capacity, dipole moments, and aromatic packing, which can be reflected in the physicochemical properties of peptide analogs. The Fmoc-protected format facilitates incorporation into defined sequences, producing well-characterized intermediates for downstream analog synthesis and comparative SAR datasets.
3. Side-Chain Functionalization
Fmoc-2,4-Difluoro-D-Phenylalanine is suitable for side-chain functionalization programs in synthetic organic chemistry that exploit aryl fluorine as a site-selective transformation handle. The difluoro-substituted phenyl ring can participate in cross-coupling and nucleophilic aromatic substitution strategies after peptide assembly or at the intermediate stage, enabling conversion into aryl-substituted derivatives while preserving the D-amino acid stereocenter. The Fmoc group supports controlled deprotection to reveal the free amine for conjugation or for generating peptide fragments that can be further modified. The resulting functionalized fluorinated amino acid derivatives can be used to access chemical space around fluorinated aromatics for fragment screening, medicinal chemistry intermediate preparation, and targeted scaffold diversification.
4. Chemical Biology Probes
Fmoc-2,4-Difluoro-D-Phenylalanine is employed in chemical biology research where fluorinated aromatic residues are incorporated to modulate molecular recognition and to support labeling-compatible peptide designs. The Fmoc-protected amino group enables controlled incorporation into peptides that can later be coupled to affinity tags, reporters, or biophysical probes through standard peptide chemistry. The difluoro phenyl side chain can function as a stable, electronically tuned motif that may influence binding orientation and can serve as a structural tracer in comparative studies of analog series. The D-amino acid stereochemistry supports investigations into enzyme selectivity, binding stereospecificity, and non-natural peptide behavior in biochemical assays without altering the core coupling workflow.
5. Pharmaceutical Manufacturing Intermediates
Fmoc-2,4-Difluoro-D-Phenylalanine is relevant to pharmaceutical intermediate preparation and process chemistry for manufacturing fluorinated peptide building blocks and defined stereochemical analogs. The Fmoc protection provides a robust handling format for controlled deprotection and coupling during peptide assembly, aligning with scalable protected amino acid synthesis practices. The difluoro-substituted aromatic ring contributes to chemical stability under typical peptide processing conditions and can be carried through to final drug-like peptide intermediates or peptidomimetic precursors. The compound's chiral D-configuration supports consistent stereochemical outcomes across batch production, enabling reproducible downstream synthesis of fluorinated peptide intermediates used in industrial fine chemical production.
6. Analytical Standards Development
Fmoc-2,4-Difluoro-D-Phenylalanine is used for analytical research and method development where fluorinated amino acid standards improve detection and characterization of peptide fragments. The presence of two fluorine atoms on the aromatic ring can enhance mass spectrometric distinguishability and support targeted analytical workflows for fluorinated peptide components. The defined D-stereochemistry and Fmoc-protected identity enable consistent reference material preparation for monitoring deprotection, coupling completeness, and impurity profiles in peptide synthesis development. The resulting analytical standards can be applied to quality-by-design studies, characterization of fluorinated analog libraries, and verification of stereochemical integrity in amino acid derivative manufacturing.
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