Fmoc-4-Chloro-D-Phenylalanine

Fmoc-4-Chloro-D-Phenylalanine is an Fmoc-protected D-phenylalanine derivative bearing a para-chloro substituent on the aromatic side chain, providing a defined chiral amino acid building block for peptide and peptidomimetic synthesis. The molecule contains a stable N-(9H-fluoren-9-ylmethoxycarbonyl) protecting group on the α-amine, a free carboxyl functionality (or carboxyl equivalent depending on supplier form) for coupling chemistry, and a chlorinated phenyl ring that can participate in halogen-directed reactivity and downstream functional transformations. The stereochemistry is fixed at the α-carbon in the D-configuration, enabling controlled incorporation of mirror-image amino acid residues into peptide scaffolds and structure-activity relationship studies. The aryl chloride also modulates polarity and electronic properties, supporting synthetic planning for aryl functionalization, conjugation handles, and analytical differentiation in amino acid derivative workflows.

1. Peptide Synthesis

Fmoc-4-Chloro-D-Phenylalanine is used in automated and solution-phase peptide synthesis where Fmoc chemistry supports stepwise N-terminal assembly. The Fmoc-protected α-amine and the D-configuration provide stereochemically defined coupling partners, while the para-chloro phenyl side chain remains compatible with typical peptide coupling conditions and can be carried through multiple synthetic steps. The chlorinated aromatic ring can serve as a stable residue during chain elongation and can later enable side-chain derivatization routes such as aryl substitution or coupling-based modifications. Downstream, the resulting peptides and peptide fragments can be applied in backbone stereochemistry studies and peptidomimetic library construction, linking amino acid derivatization to peptide coupling chemistry.

2. Peptidomimetic SAR Studies

Fmoc-4-Chloro-D-Phenylalanine is applied in SAR-focused medicinal chemistry programs that require D-amino acid incorporation and controlled side-chain electronics. The para-chloro substituent on the phenyl ring provides a handle for tuning hydrophobicity, steric profile, and aromatic reactivity without altering the α-amino acid core. The Fmoc-protected form enables consistent peptide analog assembly, allowing systematic variation of stereochemistry and aromatic substitution patterns across analog series. The chlorinated aromatic residue can further support later scaffold diversification, enabling synthesis of analogs for binding-site mapping, conformational probing, and structure-activity relationship studies in peptidomimetic design.

3. Side-Chain Functionalization

Fmoc-4-Chloro-D-Phenylalanine is suitable for synthetic organic chemistry workflows that leverage aryl chloride chemistry for post-coupling modification. The para-chloro substituent can undergo nucleophilic aromatic substitution or transition-metal-catalyzed cross-coupling after peptide assembly or after selective deprotection, enabling conversion of the side chain into alternative aryl, heteroaryl, or substituted aromatic motifs. The presence of the Fmoc group allows orthogonal protection logic during intermediate preparation, while the defined D-stereocenter maintains stereochemical integrity through functional group transformations. The chlorinated aromatic amino acid thus functions as a chiral intermediate for generating functionalized peptide building blocks and diversified peptidomimetic fragments used in downstream molecular design campaigns.

4. Chemical Biology Probes

Fmoc-4-Chloro-D-Phenylalanine is used in chemical biology research to construct D-amino acid-containing peptides and probe scaffolds with defined aromatic substitution patterns. The Fmoc-protected α-amine supports reliable incorporation into peptide sequences, and the D-configuration can be exploited to probe protease stability and stereochemical recognition in biochemical assays. The chlorinated phenyl side chain can serve as a chemically stable reporter element during labeling workflows or as a precursor for installing bioorthogonal or affinity-modulating substituents via aryl chloride functionalization. The resulting peptide probes can be applied to investigate binding interactions, molecular recognition, and functional effects of side-chain electronics and stereochemistry in biochemical research intermediate development.

5. Pharmaceutical Manufacturing

Fmoc-4-Chloro-D-Phenylalanine is relevant to pharmaceutical manufacturing and fine-chemical production routes that require chiral, protected amino acid intermediates for controlled peptide or peptide-like ingredient synthesis. The Fmoc protecting group supports standardized N-protection/deprotection cycles compatible with industrial peptide manufacturing operations, while the D-stereochemistry provides a defined mirror-image residue for consistent material attributes in peptide-based intermediates. The para-chloro aromatic side chain can be carried through manufacturing steps as a stable functionality, with later conversion to alternative substituents planned as part of a synthetic route to final active or intermediate forms. The compound therefore serves as a process-compatible chiral building block for producing peptide intermediates, enabling scalable amino acid derivative synthesis and downstream functional molecule generation.

6. Analytical Research Standards

Fmoc-4-Chloro-D-Phenylalanine is used in analytical research to prepare reference materials and method development standards for amino acid derivative characterization. The combination of Fmoc protection and a chlorinated aromatic side chain provides distinctive chromatographic and spectroscopic signatures that can aid in distinguishing D-phenylalanine-based residues from L analogs and from non-halogenated phenylalanine derivatives. The fixed stereochemistry and defined substitution pattern support quantitative and qualitative analytical workflows such as LC-MS method validation for peptide fragments and amino acid building blocks. The compound can also be employed as a chiral synthetic intermediate for generating labeled or structurally matched standards used in peptide coupling chemistry verification and structural confirmation in applied product development.

1. cRGD-functionalized, DOX-conjugated, and 64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging

2. Extended exenatide administration enhances lipid metabolism and exacerbates pancreatic injury in mice on a high fat, high carbohydrate diet

3. Urinary Metabolites Associated with Blood Pressure on a Low-or High-Sodium Die

4. Adipose tissue is a key organ for the beneficial effects of GLP-2 metabolic function

5. Exosomes-mediated Transfer of miR-125a/b in Cell-to-cell Communication: A Novel Mechanism of Genetic Exchange in the Intestinal Microenvironment