Cbz-3,5-Difluoro-D-Phenylalanine is a Cbz-protected, non-proteinogenic fluorinated amino acid derivative featuring a D-phenylalanine backbone with two fluorine atoms at the 3 and 5 positions of the aromatic side chain. The molecule contains a carbobenzyloxy (Cbz) protecting group on the amino functionality while retaining a free carboxylic acid, and its difluoro-substituted benzyl side chain provides increased electron-withdrawing character that can influence peptide coupling and downstream analytical behavior. In peptide synthesis and chemical biology workflows, this protected analogue is employed as a building block to introduce a difluorinated phenylalanine residue for structure-activity studies, conformational probing, and preparation of labeled or structurally modified peptides and related amino acid derivatives.
CAT No: CP13108
Cbz-3,5-Difluoro-D-Phenylalanine is a D-configuration phenylalanine derivative bearing a benzyloxycarbonyl (Cbz) protecting group on the amino functionality and two fluorine substituents at the 3,5-positions of the aromatic ring. The molecule combines a chiral α-carbon amino acid framework with an aryl ring that is strongly electron-withdrawing due to geminally positioned fluorine atoms, shaping both conformational preferences and reactivity toward electrophilic aromatic substitution and coupling-adjacent transformations. The Cbz group provides a stable N-protection handle compatible with standard peptide coupling conditions, while the carboxylic acid functionality (or its corresponding protected acid form, depending on the supplied form) supports conversion into peptide-ready intermediates. The presence of fluorinated aromatic features makes the compound a practical chiral building block for generating fluorinated amino acid analogs used in SAR-focused synthesis, isotope-labeling workflows, and downstream peptidomimetic construction.
1. Peptide Synthesis
Cbz-3,5-Difluoro-D-Phenylalanine is applied in peptide building block preparation where N-Cbz protection supports peptide coupling chemistry without exposing the amino group prematurely. The D-stereochemistry at the α-carbon enables incorporation of a stereodefined fluorinated residue into linear peptides and cyclic scaffolds, supporting studies that probe stereochemical effects on folding, proteolysis resistance, and conformational bias. The aromatic ring bearing 3,5-difluoro substitution provides a chemically robust side chain that can withstand typical coupling and deprotection sequences used for protected amino acid synthesis. Fluorinated peptides derived from this residue can serve as research-grade analogs for peptide library construction and as intermediates for further functionalization after Cbz removal.
2. Peptidomimetics And SAR
Cbz-3,5-Difluoro-D-Phenylalanine is utilized in peptidomimetic and structure-activity relationship (SAR) studies where the fluorinated phenyl side chain functions as a steric and electronic modulator. The 3,5-difluoro pattern can tune aromatic electronics and hydrogen-bonding patterns through inductive effects and altered dipole distribution, while the D-configuration supports systematic evaluation of stereochemical determinants. Cbz protection enables stepwise assembly of analogs using protected amino acid strategies, including iterative peptide coupling to generate defined fluorinated fragments. Downstream derivatives prepared from the resulting fluorinated peptides can be used to generate analog series for medicinal chemistry optimization and to support fragment-based scaffold refinement.
3. Chiral Amino Acid Intermediate
Cbz-3,5-Difluoro-D-Phenylalanine is suitable as a chiral amino acid intermediate for stereoselective synthesis routes that require a D-configured phenylalanine core. The protected amine (Cbz) and amino acid backbone allow controlled conversion into peptide-ready forms, including activation of the carboxyl functionality for subsequent coupling steps in fine chemical synthesis. The fluorinated aromatic ring provides a chemically distinctive motif that can be carried through multi-step sequences with predictable behavior under common protecting-group manipulations. The resulting fluorinated chiral intermediates can be employed to build libraries of unnatural amino acid derivatives, enabling downstream access to fluorinated peptide analogs and chiral molecular scaffolds.
4. Side-Chain Functionalization
Cbz-3,5-Difluoro-D-Phenylalanine is applied in side-chain functionalization programs where the fluorinated aromatic ring serves as a handle for generating further substituted phenyl derivatives. The electron-withdrawing fluorines can influence regioselectivity and reactivity in subsequent aromatic transformations, supporting routes to additional substituted analogs while maintaining the amino acid stereocenter. Cbz protection stabilizes the nitrogen during electrophilic or nucleophilic aromatic modification steps, allowing the compound to act as a protected amino acid precursor in multi-functional synthesis. Fluorinated derivatives prepared from this intermediate can feed into materials-oriented chemistry and specialty fine chemical production where controlled aromatic substitution patterns are required.
5. Pharmaceutical Manufacturing Intermediates
Cbz-3,5-Difluoro-D-Phenylalanine is relevant to pharmaceutical manufacturing workflows that involve fluorinated building blocks for peptide-like active ingredients or process intermediates. The Cbz-protected amino group supports compatibility with standard solid-phase or solution-phase peptide assembly logic, enabling controlled deprotection and coupling sequence design during manufacturing-scale synthesis planning. The fluorinated aryl side chain can be maintained throughout upstream steps to preserve defined physicochemical properties that are often targeted in process development for fluorinated intermediates. Downstream formation of fluorinated peptide intermediates and peptidomimetic fragments from this compound aligns with industrial fine chemical synthesis needs for stereochemically defined amino acid derivatives.
6. Analytical Research Standards
Cbz-3,5-Difluoro-D-Phenylalanine is employed in analytical research as a defined fluorinated amino acid standard for method development and characterization of peptide hydrolysates or fluorinated analog mixtures. The combination of a protected amino acid structure and a distinctive 3,5-difluorophenyl motif provides strong analytical discriminability in chromatographic and mass spectrometric workflows. Cbz protection supports consistent handling during sample preparation when comparing protected versus deprotected species, enabling robust interpretation of coupling and deprotection outcomes in peptide synthesis studies. The compound can be used to generate reference materials for verifying stereochemical incorporation of D-configured residues and for supporting quality control of fluorinated peptide building block preparations.
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