Fmoc-D-phenylglycine(4-OtBu) is a protected, non-natural amino acid derivative featuring a D-configuration at the alpha carbon and a phenylglycine side chain substituted with a tert-butyl ether at the 4-position. The molecule bears an Fmoc (9H-fluoren-9-ylmethoxycarbonyl) group on the amino functionality and a carboxyl group available for peptide-coupling chemistry, while the 4-OtBu substituent masks the corresponding phenolic oxygen to modulate polarity and chemoselectivity during synthesis. In peptide chemistry and chemical biology, it is used as a building block for incorporating the phenylglycine motif and the protected aromatic oxygen into peptides or peptide-related intermediates, supporting controlled stepwise assembly and subsequent deprotection to reveal the functionalized aromatic handle.
CAT No: CP09808
Fmoc-D-phenylglycine(4-OtBu) is a D-configured, Fmoc-protected phenylglycine derivative bearing a tert-butyl-protected phenolic group at the 4-position of the aromatic ring. The molecule combines an N-Fmoc carbamate for orthogonal amine protection with a chiral alpha-carbon that supports stereochemically defined peptide coupling, while the 4-OtBu ether functions as a removable protecting group for the phenol. The aromatic side chain provides a hydrophobic, pi-interacting handle, and the protected phenolic oxygen can be unmasked under controlled deprotection conditions to regenerate a reactive phenol for subsequent derivatization. As a chiral amino acid intermediate, it participates in standard protected amino acid chemistry and can be carried through peptide synthesis workflows to furnish defined aromatic substitution patterns in downstream analogs.
1. Peptide Synthesis
Fmoc-D-phenylglycine(4-OtBu) is used in peptide building and solid-phase peptide synthesis workflows where Fmoc protection enables stepwise N-terminal deprotection and coupling. The D-stereocenter at the alpha-carbon supports stereochemically defined incorporation of the phenylglycine residue, while the aromatic ring provides conformational and side-chain interaction features relevant to peptide folding and binding-site mimicry. The 4-OtBu group protects the phenolic oxygen during coupling and chain assembly, preventing side reactions such as phenol-mediated acylation or oxidative processes. After peptide assembly, phenol deprotection can generate a free 4-hydroxy functionality for further functionalization, enabling preparation of aromatic phenol-containing peptides and peptide analogs for structure-activity relationship studies. The compound therefore serves as a stereopure, protected amino acid building block for constructing defined aromatic and phenolic substitution patterns in peptide science.
2. Side-Chain Functionalization
Fmoc-D-phenylglycine(4-OtBu) is applied to side-chain engineering in medicinal chemistry and chemical biology programs that require controlled presentation of a phenolic handle on an amino acid scaffold. The tert-butyl ether at the 4-position stabilizes the phenolic oxygen during earlier synthetic steps, including peptide coupling chemistry and protecting-group juggling, while the aromatic ring maintains a rigid, pi-rich environment for molecular recognition. Phenol unmasking can enable downstream transformations such as etherification, esterification, or conjugation strategies that depend on selective reactivity of the regenerated hydroxyl group. Incorporation into peptides or peptidomimetics can then position the phenol for hydrogen-bonding interactions or for attachment of probes, linkers, or affinity motifs. This makes the compound suitable for amino acid derivatization routes that connect protected amino acid synthesis with later functional group installation on the aromatic side chain.
3. Chemical Biology Probes
Fmoc-D-phenylglycine(4-OtBu) supports chemical biology and biomolecular labeling efforts that rely on orthogonally protected residues to control when reactive groups appear. The Fmoc carbamate enables clean handling as an N-protected amino acid derivative during synthesis of labeled peptides, while the D-configuration provides stereochemical control that may influence probe conformation and recognition by target proteins or receptors. The 4-OtBu protecting group permits phenol-bearing probe generation after assembly, allowing timed exposure of the phenolic oxygen for conjugation to electrophiles, linkers, or affinity tags. The aromatic phenylglycine framework can also serve as a hydrophobic anchor within probe scaffolds, supporting membrane-associated or binding-site localization depending on the overall design. As a result, the compound can be employed as a chiral intermediate for generating phenol-functional peptide probes and related chemical biology reagents.
4. Peptidomimetics And SAR
Fmoc-D-phenylglycine(4-OtBu) is relevant to peptidomimetic construction and structure-activity relationship studies where aromatic amino acid residues are used to tune binding interactions and conformational preferences. The phenylglycine motif introduces a stereodefined alpha-carbon and an aromatic side chain that can be retained in non-natural peptide analogs, helping maintain key interaction geometry while varying other functional elements. The protected phenol at the 4-position supports synthesis of analog libraries by reducing undesired phenolic reactivity during fragment assembly, coupling, and purification steps. Deprotection enables consistent installation of a free hydroxyl group across a series, supporting comparative SAR evaluation of hydrogen-bonding capacity and aromatic substitution effects. This use case links protected amino acid derivative chemistry with downstream molecular scaffold generation for systematic SAR studies.
5. Pharmaceutical Intermediate Preparation
Fmoc-D-phenylglycine(4-OtBu) is suitable for industrial fine chemical synthesis routes that require chiral, protected amino acid intermediates for downstream manufacture of peptide-derived intermediates. The Fmoc-protected amine and the tert-butyl-protected phenol provide orthogonal protection elements that can be managed in batch or continuous synthesis strategies to maintain functional-group integrity through multiple transformations. The stereochemical integrity of the D-phenylglycine center supports production of defined chiral building blocks used in process chemistry intermediate preparation for peptide and peptidomimetic manufacturing. The aromatic side chain and protected phenolic oxygen can be carried into subsequent steps where controlled deprotection and functionalization generate the target substitution pattern. Accordingly, the compound can serve as a chiral amino acid intermediate for specialty chemical production workflows that depend on reliable protecting-group behavior and stereopure amino acid incorporation.
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