N-(2-Pyrazinylcarbonyl)-L-phenylalanine
[CAS# 114457-94-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrazines
• Name: N-(2-Pyrazinylcarbonyl)-L-phenylalanine
• Synonyms: (2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoic acid
• Molecular Formula: C₁₄H₁₃N₃O₃
• Molecular Weight: 271.27
• CAS Registry Number: 114457-94-2
• SMILES: C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)C2=NC=CN=C2

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*, 1.323 g/mL (Expl.)
• Melting point: 166-169 °C (Expl.)
• Boiling point: 573.8±50.0 °C 760 mmHg (Calc.)^*
• Flash point: 300.8±30.1 °C (Calc.)^*
• Index of refraction: 1.613 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

N-(2-Pyrazinylcarbonyl)-L-phenylalanine is an amide compound formed by the condensation of 2-pyrazinecarboxylic acid and the amino acid L-phenylalanine. Its molecular formula is C₁₄H₁₃N₃O₃. Structurally, it consists of a pyrazine ring bearing a carboxamide linkage to the α-amino group of L-phenylalanine, which retains its chiral center and unmodified side chain containing a phenyl group.

The synthesis of this compound typically involves activation of the carboxylic acid group on 2-pyrazinecarboxylic acid using standard peptide-coupling reagents such as carbodiimides (e.g., EDC or DCC), often in the presence of an additive like HOBt or NHS, followed by reaction with the free amine of L-phenylalanine. Protection of the carboxyl group of the amino acid is generally not required, as selective acylation occurs at the amino group under controlled conditions.

N-(2-Pyrazinylcarbonyl)-L-phenylalanine belongs to a class of heteroaryl-amino acid conjugates often investigated for their potential biological activity. The pyrazine ring is an electron-deficient heteroaromatic moiety frequently encountered in medicinal chemistry, particularly in drug design targeting enzyme active sites or protein-ligand binding domains. When attached to amino acids, such heterocycles can improve receptor binding affinity, bioavailability, and metabolic stability.

Compounds of this type may be studied as enzyme inhibitors, receptor ligands, or intermediates in the synthesis of bioactive molecules. In particular, the presence of the L-phenylalanine residue may aid in molecular recognition by proteins due to its aromatic and hydrophobic properties, while the pyrazinyl group can participate in hydrogen bonding, metal coordination, or π-stacking interactions.

The physicochemical properties of N-(2-pyrazinylcarbonyl)-L-phenylalanine reflect its amphiphilic nature. It is typically a solid at room temperature and shows moderate solubility in water and polar organic solvents such as methanol, ethanol, or dimethyl sulfoxide. The molecule has both acidic and basic functional groups, including a carboxylic acid and an amide, which contribute to solubility and ionization behavior at physiological pH.

Spectroscopic characterization includes diagnostic signals in NMR for the aromatic protons of the phenylalanine side chain and the pyrazine ring, as well as IR absorption bands characteristic of the amide carbonyl group and carboxylic acid. Mass spectrometry confirms the molecular weight and helps assess purity and fragmentation patterns.

Due to its chiral center, the compound exists in a single enantiomeric form derived from naturally occurring L-phenylalanine. Optical rotation and chiral chromatographic techniques are typically used to confirm enantiomeric purity and absolute configuration.

In summary, N-(2-pyrazinylcarbonyl)-L-phenylalanine is a heteroaryl-amino acid conjugate featuring a pyrazinecarboxamide linked to the α-amino group of L-phenylalanine. It is of interest in synthetic and medicinal chemistry for its structural features and potential bioactivity, serving as an intermediate or scaffold in the design of pharmacologically active molecules.

References

2020. Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo. Journal of Medicinal Chemistry, 63(5).
DOI: 10.1021/acs.jmedchem.9b01746