H-2,6-Difluoro-Phe-OH · HCl

H-2,6-Difluoro-Phe-OH · HCl is a chiral amino acid derivative corresponding to 2,6-difluorinated phenylalanine, present as the hydrochloride salt. The molecule contains a primary amino group as the protonated ammonium chloride, a carboxylic acid suitable for activation and peptide coupling, and a side-chain aromatic ring bearing two fluorine atoms at the ortho positions that modulate electronics, steric profile, and metabolic stability in downstream analogs. The 2,6-difluoro substitution pattern can influence hydrogen-bonding interactions and conformational preferences of peptide backbones and side-chain environments, while the salt form improves handling of the amino acid in synthesis and intermediate preparation. The combination of a stereogenic α-carbon with a functionalized aryl side chain makes the compound a practical chiral building block for protected amino acid chemistry and for generating fluorinated peptidomimetics and SAR-focused libraries.

1. Peptide Synthesis

H-2,6-Difluoro-Phe-OH · HCl is applied in peptide building and solid-phase or solution-phase coupling workflows where a Cα stereocenter and carboxylic acid enable amide bond formation. The hydrochloride form provides a defined amino functionality for conversion into an N-protected amino acid derivative, while the carboxyl group can be activated to support peptide coupling chemistry. The 2,6-difluoro phenyl side chain participates in side-chain-specific recognition and can be retained through standard coupling and deprotection sequences to generate fluorinated peptide segments. Downstream, the resulting peptide products serve as research-grade analogs for mapping how ortho-fluorination affects conformation, binding interfaces, and stability in peptide science.

2. SAR Studies

H-2,6-Difluoro-Phe-OH · HCl is used in structure-activity relationship studies and molecular design campaigns that require systematic incorporation of fluorinated aromatic residues. The ortho difluoro substitution pattern on the phenylalanine side chain provides a handle for tuning lipophilicity, dipole effects, and steric shielding around the aromatic ring. The amino acid's defined stereochemistry supports consistent placement at peptide positions, enabling comparative evaluation of analogs where only side-chain electronics and sterics change. The compound can be converted into protected derivatives for library synthesis, supporting generation of fluorinated SAR panels and fragment-like peptide mimetics.

3. Protected Amino Acids

H-2,6-Difluoro-Phe-OH · HCl is suitable for protected amino acid synthesis workflows that require controlled N- and C-terminal functionality. The amino acid hydrochloride can be neutralized and then transformed into N-protected forms compatible with peptide coupling reagents, while the carboxylic acid can be maintained or temporarily masked depending on the intended coupling strategy. The presence of strongly electron-withdrawing fluorines on the aromatic ring can influence subsequent derivatization steps and may be advantageous when preparing intermediates for peptidomimetic construction or late-stage functional group compatibility. Downstream, the protected amino acid derivatives derived from this compound support scalable intermediate preparation for peptide building block supply chains and fine chemical synthesis routes.

4. Peptidomimetics And Analogues

H-2,6-Difluoro-Phe-OH · HCl is applied in peptidomimetic construction where fluorinated aromatic residues are incorporated to modulate binding conformations and physicochemical properties of analog scaffolds. The α-amino acid framework enables incorporation into constrained or modified backbones through amide formation and subsequent functional group transformations. The difluoro-substituted phenyl ring can serve as a stereoelectronic element that alters aromatic interactions and can be carried into downstream synthetic steps such as side-chain elaboration or scaffold cyclization. The resulting fluorinated analogs can be used as biochemical research intermediates and molecular probes for evaluating structure-function relationships in peptide-like systems.

5. Process Chemistry Intermediate

H-2,6-Difluoro-Phe-OH · HCl is employed as a chiral amino acid intermediate in process chemistry and specialty chemical production where robust handling of amino acid salts supports manufacturing-scale synthesis. The hydrochloride salt provides a practical form for storage and metering, while the free carboxylic acid and amino functionality support conversion into activated coupling-ready derivatives during manufacturing route design. The 2,6-difluoro aromatic side chain remains chemically stable under typical protection and activation conditions, enabling consistent downstream incorporation into peptide intermediates and fluorinated fine chemicals. Downstream utility includes preparation of fluorinated amino acid derivatives for controlled supply into peptide synthesis operations and for producing research-grade fluorinated intermediates used in industrial chemical manufacturing.

1. Novel Peptide-Based PD1 Immunomodulators Demonstrate Efficacy in Infectious Disease Vaccines and Therapeutics

2. Immune responses to homocitrulline-and citrulline-containing peptides in rheumatoid arthritis

3. Relatedness of antibodies to peptides containing homocitrulline or citrulline in patients with rheumatoid arthritis

4. Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors

5. Genetic, cellular, and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore