(S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic Acid: Properties & Uses
(S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic Acid: Properties & Uses
(S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic acid is a enantiomerically defined β-amino acid building block featuring a meta-trifluoromethyl aromatic substituent, widely valued in medicinal chemistry and asymmetric synthesis for its unique combination of stereochemical purity and fluorine-mediated physicochemical properties.
- Chemical Name
- (S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic acid
- SKU
- A709981
- Compound Class
- Chiral β-amino acid
- Stereochemistry
- S-configuration (single enantiomer)
- Key Functional Groups
- Primary amine, carboxylic acid, trifluoromethyl aryl
- Primary Application
- Pharmaceutical intermediate and peptidomimetic building block
Chemical Identity and Structure
(S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic acid belongs to the class of β3-amino acids, in which the amino group is positioned at the β-carbon relative to the carboxylic acid. This structural motif distinguishes it from proteinogenic α-amino acids and confers distinct conformational properties that are of significant interest in drug design and chemical biology.
The compound carries a meta-trifluoromethyl (CF3) substituent on the phenyl ring. The trifluoromethyl group is a strongly electron-withdrawing moiety that profoundly influences the aromatic ring's electronic character, increasing metabolic stability relative to non-fluorinated analogues and modulating lipophilicity (log P). The S-configuration at the β-carbon provides defined stereochemistry, which is critical for enantioselective interactions with biological targets.
The bifunctional nature of the molecule — bearing both a free amine and a carboxylic acid — allows it to participate in amide bond formation, esterification, reductive amination, and N-protection/deprotection sequences, making it a versatile synthon in multi-step synthetic routes.
Role in Medicinal Chemistry and Drug Discovery
β-Amino acids have emerged as important scaffolds in medicinal chemistry due to their resistance to proteolytic degradation compared with α-amino acid counterparts. Incorporating a β-amino acid residue into a peptide or peptidomimetic sequence can dramatically improve in vivo stability, oral bioavailability, and the ability to cross biological membranes. (S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic acid is particularly attractive because the aryl-substituted β3-amino acid framework mimics phenylalanine-like pharmacophores while adding the metabolic and electronic advantages of the CF3 group.
The meta-CF3 phenyl moiety is frequently encountered in FDA-approved drugs and clinical candidates, where it contributes to target binding affinity through hydrophobic and electrostatic interactions, while simultaneously blocking cytochrome P450-mediated aromatic hydroxylation. This makes the compound a highly relevant building block for lead optimization campaigns targeting CNS disorders, oncology, and infectious diseases, among other therapeutic areas.
In asymmetric synthesis, the single enantiomer form ensures that chirality transfer to downstream intermediates is predictable and controlled, which is essential for meeting regulatory requirements for stereochemically pure active pharmaceutical ingredients (APIs).
Synthetic Utility and Handling Considerations
(S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic acid can serve as a direct coupling partner in solid-phase peptide synthesis (SPPS) after appropriate N-protection (e.g., Fmoc or Boc chemistry), or as a solution-phase intermediate for the construction of β-lactams, heterocyclic scaffolds, and other nitrogen-containing pharmacophores. Its free carboxylic acid is amenable to standard activation reagents such as HATU, EDC/HOBt, or thionyl chloride, enabling efficient amide bond formation.
When used in enantioselective transformations or as a chiral auxiliary component, care should be taken to avoid racemization at the β-stereocenter, particularly under strongly basic or acidic conditions at elevated temperatures. Standard laboratory practices for handling β-amino acids apply: the compound should be stored in a cool, dry environment, protected from moisture and light, and handled with appropriate personal protective equipment given the presence of the trifluoromethyl aryl group.
Researchers should confirm purity (typically assessed by HPLC and optical rotation) and enantiomeric excess (ee) prior to use in asymmetric synthesis to ensure reproducibility of chiral outcomes. Aladdin Scientific supplies this compound as SKU A709981 for research use.
Quality, Purity, and Ordering Information
For research applications requiring stereochemical fidelity, sourcing enantiopure β-amino acid building blocks from a reliable supplier is essential. Aladdin Scientific offers (S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic acid under SKU A709981. Researchers and procurement teams are encouraged to consult the product specification sheet for detailed information on purity grade, enantiomeric excess, melting point, optical rotation, and recommended storage conditions prior to placing an order.
When evaluating reagent grade suitability, consider the downstream application: synthesis of APIs or advanced intermediates typically demands higher purity grades and documented ee values, whereas exploratory medicinal chemistry screening may accommodate lower-grade material. Aladdin Scientific's technical support team can assist in selecting the appropriate specification for your research needs.
Orders for A709981 can be placed through the Aladdin Scientific website or authorized distributors. For bulk quantities or custom purity specifications, contact the Aladdin Scientific sales team directly to discuss tailored supply arrangements.
Frequently asked questions
What distinguishes (S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic acid from the corresponding α-amino acid?
Unlike α-amino acids, where the amine is directly attached to the carbon bearing the carboxyl group, this compound is a β-amino acid in which an additional methylene unit separates the amine from the carboxylate. This structural difference confers resistance to most proteolytic enzymes that cleave α-peptide bonds, making β-amino acid residues valuable for improving peptide stability in biological environments.
Why is the S-configuration important for this compound's use in pharmaceutical synthesis?
Enantiomers of chiral building blocks can interact very differently with biological targets, often exhibiting distinct pharmacological activity, potency, or toxicity profiles. Using the single S-enantiomer ensures predictable stereochemical outcomes in downstream transformations and is essential for producing stereochemically defined APIs that comply with regulatory agency guidelines on chiral drug substances.
How should (S)-3-Amino-3-(3-(trifluoromethyl)phenyl)propanoic acid be stored to maintain its integrity?
As a general best practice for amino acid derivatives, this compound should be stored in a tightly sealed container in a cool, dry location away from moisture, light, and oxidizing agents. Researchers should consult the Aladdin Scientific product specification sheet (SKU A709981) for the supplier-recommended storage temperature and shelf-life data specific to this lot.
Can this compound be used directly in solid-phase peptide synthesis?
Yes, after N-protection of the free amine with a compatible protecting group such as Fmoc or Boc, the compound can be incorporated into SPPS workflows using standard carboxyl-activation reagents. The carboxylic acid terminus couples to resin-bound amines under conditions analogous to those used for standard α-amino acid building blocks.
References
- Seebach, D.; Gardiner, J. Beta-peptidic peptidomimetics. Accounts of Chemical Research, 2008.
- Juaristi, E.; Soloshonok, V. A. (Eds.) Enantioselective Synthesis of Beta-Amino Acids, 2nd ed. Wiley-VCH, 2005.
- Muller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: Looking beyond intuition. Science, 2007, 317, 1881-1886.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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