Fmoc-2,6-Difluoro-D-Phenylalanine is a protected, non-natural amino acid derivative in which the phenylalanine scaffold bears two fluorine atoms at the 2- and 6-positions of the aromatic ring and the amino acid stereochemistry is specified as D. The molecule contains an Fmoc-protected amino group alongside a free carboxylic acid, with the fluorinated benzyl side chain providing increased electron-withdrawing character and altered hydrophobic/aromatic interaction properties relative to unsubstituted phenylalanine. It is used as a building block for stepwise peptide synthesis and for structure-activity or chemical biology studies where incorporation of a fluorinated, stereodefined phenylalanine analogue enables controlled modulation of aromatic-ring electronics and labeling-compatible chemical characterization.
CAT No: CP12907
Fmoc-2,6-Difluoro-D-Phenylalanine is an Fmoc-protected D-phenylalanine derivative bearing two fluorine atoms at the 2- and 6-positions of the aromatic ring. The molecule combines a stereodefined α-amino acid core (D-configuration) with an Fmoc carbamate that supports base-stable handling and on-demand deprotection during solid-phase peptide synthesis. The difluoro-substituted phenyl side chain introduces distinct electronic effects, increased hydrophobicity, and altered aromatic reactivity compared with unsubstituted phenylalanine, while the fluorine atoms provide handles for downstream derivatization, spectroscopic tracking, and conformational tuning in peptide contexts. The resulting chiral, protected amino acid building block is suitable for coupling chemistry that preserves stereochemical integrity and enables incorporation into peptide analogs and fluorinated molecular scaffolds.
1. Peptide Synthesis
Fmoc-2,6-Difluoro-D-Phenylalanine is applied in peptide building block preparation for solid-phase and solution-phase peptide synthesis where a D-amino acid residue is required. The Fmoc-protected α-amino group participates in standard peptide coupling after Fmoc removal, while the carboxylate functionality enables amide bond formation to neighboring residues. The 2,6-difluoro aromatic side chain can modulate local sterics and electronics, supporting the construction of fluorinated peptide analogs used to probe folding, stability, and binding-site complementarity. The stereodefined D-configuration helps generate predictable sequence stereochemistry for peptide materials and biochemical research reagents. Amino acid chemistry compatibility is maintained through the protected amine strategy and the robust aromatic fluorination pattern that survives typical peptide assembly conditions.
2. Peptidomimetics And SAR
Fmoc-2,6-Difluoro-D-Phenylalanine supports peptidomimetic construction and structure-activity relationship studies by enabling incorporation of a difluoroaryl side chain into constrained peptide-like scaffolds. The difluoro substitution at the 2,6-positions can influence aromatic ring orientation, hydrogen-bonding patterns, and dipole distribution, which are often critical parameters in medicinal chemistry SAR workflows. The D-amino acid stereochemistry provides access to non-natural backbone configurations that may alter protease susceptibility and conformational preferences in peptide analog series. Fmoc-based synthesis compatibility facilitates rapid generation of analog libraries through controlled coupling and sequence-defined assembly. The resulting fluorinated residue can serve as a chemically defined motif for downstream analog comparison and mechanistic interpretation in applied SAR programs.
3. Chemical Biology Probes
Fmoc-2,6-Difluoro-D-Phenylalanine is utilized in chemical biology research to generate fluorinated peptide probes for studying biomolecular interactions and microenvironment effects. The aromatic difluoro pattern can function as a spectroscopically informative substituent, enabling tracking of incorporation into peptides and supporting interpretation of binding-induced changes in chemical environments. The Fmoc-protected amino acid format enables site-specific incorporation into peptide sequences, including peptide tags used in pull-down experiments, affinity reagents, or substrate mimics for enzymology. The D-configuration can help reduce enzymatic degradation pathways associated with protease recognition motifs, enabling longer-lived probe formats in biochemical assay development. Amino acid derivative chemistry is directly leveraged through the protected amine and carboxyl functionalities that support reproducible peptide assembly.
4. Protein Engineering
Fmoc-2,6-Difluoro-D-Phenylalanine is relevant to protein engineering workflows that require incorporation of non-natural amino acid residues into peptide segments or protein domains. The protected amino acid structure supports controlled synthesis of modified peptides that can be used as building blocks for protein fragment assembly, domain mapping, or receptor-binding studies. The difluoroaryl side chain can introduce localized steric bulk and electronic modulation relative to standard phenylalanine, enabling systematic evaluation of how aromatic substitution affects binding interfaces and conformational stability. The D-stereocenter supports creation of stereochemically defined variants that can be compared across engineered constructs. Downstream utility extends to generating sequence-defined fluorinated fragments suitable for biochemical characterization and materials-oriented protein analog development.
5. Pharmaceutical Intermediate Preparation
Fmoc-2,6-Difluoro-D-Phenylalanine is suitable for pharmaceutical intermediate preparation where fluorinated, stereodefined amino acid derivatives are required for downstream synthesis of peptide-like drug candidates or advanced intermediates. The Fmoc-protected α-amino acid format provides a protected amine strategy that can be carried through multistep synthetic sequences and then converted into peptide coupling-ready forms under controlled deprotection conditions. The 2,6-difluoro aromatic functionality can serve as a medicinal chemistry motif to tune physicochemical properties such as lipophilicity and aromatic electronic character in final active or intermediate structures. The D-configuration supports stereochemically consistent analog series, which is important for scalable manufacturing of defined stereoisomeric intermediates. Industrial relevance is supported by the compound's compatibility with peptide coupling chemistry and its role as a chiral building block in fine chemical synthesis routes.
6. Process Chemistry And Fine Chemical Synthesis
Fmoc-2,6-Difluoro-D-Phenylalanine is employed in process chemistry and fine chemical synthesis for manufacturing fluorinated amino acid derivatives and peptide intermediates with controlled stereochemistry. The Fmoc carbamate provides a stable protecting group that can be removed on demand, supporting streamlined process design for protected amino acid handling and subsequent coupling steps. The presence of the difluoro-substituted aromatic ring can influence crystallinity and physicochemical behavior, which may be leveraged during intermediate isolation and solid handling in manufacturing workflows. The amino acid's defined D-configuration supports consistent stereochemical outcomes across batch production of peptide building blocks and analog precursors. Downstream formation of peptide-linked structures, peptidomimetics, and fluorinated molecular scaffolds is enabled through the combination of protected amine chemistry and an intact carboxyl functionality suitable for coupling chemistry.
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