Fmoc-3-Chloro-D-Phenylalanine

Fmoc-3-Chloro-D-Phenylalanine is a chiral, N-(9H-fluoren-9-ylmethoxycarbonyl) protected phenylalanine derivative in which the aromatic ring bears a 3-chloro substituent and the stereocenter corresponds to the D-configuration. The molecule combines an Fmoc-protected amino group for controlled peptide coupling with a side-chain carboxylic acid functionality characteristic of amino acid building blocks, while the aryl chloride introduces a handle for subsequent cross-coupling or nucleophilic aromatic substitution chemistry. The presence of the chloro substituent modulates electronic density on the aromatic ring, which can influence reactivity during derivatization and compatibility with peptide synthesis conditions. As a chiral amino acid intermediate, it is designed to participate in protected amino acid chemistry and downstream scaffold functionalization while preserving stereochemical integrity through the protected Fmoc strategy.

1. Peptide Synthesis

Fmoc-3-Chloro-D-Phenylalanine is applied in solid-phase peptide synthesis and solution-phase peptide assembly where an Fmoc-protected amino acid is required for stepwise N-terminal deprotection and coupling. The D-configuration at the α-carbon provides stereochemical control for incorporating a defined chiral residue into peptide sequences, while the phenyl side chain bearing a 3-chloro substituent supports incorporation of aryl-functionalized motifs without premature side reactions. The aryl chloride remains available for post-coupling diversification, enabling late-stage introduction of substituted aromatic patterns after the peptide backbone is assembled. The resulting chloroaryl-containing peptides can be used as research-grade sequence variants and peptidomimetic precursors for structure-activity relationship studies and biochemical binding investigations.

2. Side-Chain Functionalization

Fmoc-3-Chloro-D-Phenylalanine supports amino acid derivatization workflows that exploit the aryl chloride as a reactive functional group for further synthetic elaboration. The 3-chloro substituent on the phenyl ring can participate in palladium-catalyzed cross-coupling to install aryl, heteroaryl, or alkyl substituents, or can undergo nucleophilic aromatic substitution under appropriate conditions to generate substituted anilines and related motifs. The Fmoc-protected nitrogen and the amino acid framework allow the compound to be carried through multi-step synthesis as a protected chiral intermediate, then converted into peptide-compatible or conjugation-ready forms after deprotection. Downstream functionalized derivatives derived from this building block can serve as molecular scaffold intermediates for medicinal chemistry, chemical biology probes, and peptidomimetic libraries.

3. Chiral Amino Acid Intermediate

Fmoc-3-Chloro-D-Phenylalanine is used as a chiral amino acid intermediate for asymmetric and stereochemically controlled synthesis of D-configured peptide building blocks. The Fmoc carbamate protects the amine during handling and coupling, helping maintain the integrity of the α-stereocenter while the side-chain aryl chloride provides a second orthogonal functional element for later diversification. The combination of a protected amine and a side-chain reactive handle enables route design in which protection, coupling, and functional-group transformation can be sequenced to minimize epimerization and side reactions. The compound can therefore be employed to construct defined stereochemical variants for SAR studies, stereochemical mapping of binding determinants, and chiral fragment generation in synthetic organic chemistry.

4. Chemical Biology Probes

Fmoc-3-Chloro-D-Phenylalanine is suitable for chemical biology research where chloroaryl amino acid residues can be incorporated into peptides or peptide-like constructs for probe development. The D-phenylalanine scaffold supports controlled incorporation into biomolecule-interacting sequences, while the 3-chloro substituent provides a chemically addressable site for subsequent conjugation chemistry or affinity-tag diversification. The Fmoc group enables reliable peptide building block preparation, allowing the chloroaryl residue to be positioned at specific locations within a peptide framework that influences recognition and stability. Chloroaryl-containing peptide probes derived from this intermediate can be used to generate structure-defined reagents for studying molecular interactions, mapping binding pockets, and producing labeled or derivatized biomolecular tools.

5. Pharmaceutical Manufacturing Intermediates

Fmoc-3-Chloro-D-Phenylalanine can be applied in pharmaceutical manufacturing contexts as a defined, stereochemically characterized protected amino acid intermediate for producing chloroaryl-substituted peptide intermediates. The Fmoc-protected amine and amino acid architecture support standardized peptide coupling operations, while the aryl chloride enables controlled downstream functionalization steps that can be integrated into process chemistry to reach substituted aromatic targets. The D-stereochemistry provides a predictable stereochemical outcome for manufacturing routes that require specific enantiomeric composition in peptide-based intermediates. The compound thus functions as a process-compatible building block for specialty chemical production where peptide analogs and functionalized amino acid derivatives are manufactured for research-grade and industrial-grade supply chains.

1. A possible role of tachykinin-related peptide on an immune system activity of mealworm beetle, Tenebrio molitor L

2. P-selectin and Complement’s Role in a Neonatal Model of Germinal Matrix Hemorrhage-Induced Secondary Injury

3. Sex differences in oxidative stress level and antioxidative enzymes expression and activity in obese pre-diabetic elderly rats treated with metformin or liraglutide

4. Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

5. C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy