Boc-Tyr(tBu)-Aib-OH
[CAS# 2639221-78-4]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives
• Name: Boc-Tyr(tBu)-Aib-OH
• Synonyms: 2-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoyl]amino]propanoic acid; (S)-2-(3-(4-(tert-Butoxy)phenyl)-2-((tert-butoxycarbonyl)amino)propanamido)-2-methylpropanoic acid
• Protein Sequence: XX
• Molecular Formula: C₂₂H₃₄N₂O₆
• Molecular Weight: 422.52
• CAS Registry Number: 2639221-78-4
• SMILES: CC(C)(C)OC1=CC=C(C=C1)C[C@@H](C(=O)NC(C)(C)C(=O)O)NC(=O)OC(C)(C)C

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P305+351+338-P302+352

Discovory and Applicatios

Boc-Tyr(tBu)-Aib-OH is a protected dipeptide derivative that serves as a versatile building block in peptide synthesis. The compound consists of three distinct structural elements that are important in solid-phase and solution-phase peptide chemistry. The N-terminus of the molecule is protected with the Boc (tert-butyloxycarbonyl) group, a widely used protecting group that can be removed under acidic conditions, typically with trifluoroacetic acid. The first amino acid residue is tyrosine (Tyr), a natural aromatic amino acid that carries a hydroxyl group on the phenol side chain. In this molecule, the tyrosine side chain hydroxyl is protected with a tert-butyl (tBu) ether, preventing undesired side reactions during peptide coupling. The second amino acid is α-aminoisobutyric acid (Aib), a non-proteinogenic amino acid with two methyl groups at the α-carbon, which imparts strong steric effects that stabilize helical secondary structures. The C-terminus of the molecule is present as a free carboxylic acid (-OH), making it suitable for further coupling reactions in peptide elongation.

The discovery of Boc-Tyr(tBu)-Aib-OH as a useful synthetic intermediate stems from advances in peptide chemistry that emphasized the importance of protecting groups and conformationally restricted amino acids. Boc chemistry was introduced in the mid-20th century as one of the first systematic approaches for peptide synthesis, enabling controlled and sequential assembly of peptides. Meanwhile, Aib was recognized for its unique ability to stabilize α-helical and 3₁₀-helical conformations, even in short peptide sequences, due to steric hindrance at the α-carbon. Combining these elements, Boc-Tyr(tBu)-Aib-OH was developed as a tool for constructing peptides with defined structures and enhanced stability.

Applications of Boc-Tyr(tBu)-Aib-OH are primarily in synthetic and structural peptide chemistry. In peptide synthesis, the Boc group allows for controlled N-terminal protection and deprotection, while the tBu protection on the tyrosine side chain ensures selectivity during coupling steps. This dual protection strategy is critical for preparing peptides containing tyrosine residues, since the unprotected phenol group can otherwise undergo side reactions. The incorporation of Aib within the dipeptide unit plays an important role in enforcing helical conformations. This makes Boc-Tyr(tBu)-Aib-OH valuable in the preparation of peptides designed for structural studies or for therapeutic applications where stability and rigidity are desired.

In medicinal chemistry, Aib-containing peptides synthesized from Boc-Tyr(tBu)-Aib-OH are of interest due to their enhanced resistance to enzymatic degradation. Peptides with Aib residues often show improved pharmacokinetic properties compared to their natural counterparts, making them promising candidates for drug development. Tyrosine residues add an additional dimension, as they can participate in hydrogen bonding and π-stacking interactions, providing functional diversity. Protected intermediates such as Boc-Tyr(tBu)-Aib-OH allow chemists to introduce these features in a controlled way.

In structural biology, peptides derived from Boc-Tyr(tBu)-Aib-OH are employed as model systems to study protein folding, stability, and conformational transitions. The combination of tyrosine and Aib residues provides a useful balance between natural amino acid functionality and conformational restriction, making them suitable for spectroscopic analysis using circular dichroism, fluorescence, or NMR. These studies help elucidate the role of side-chain interactions and steric effects in determining secondary structure.

Beyond medicinal and structural biology applications, Boc-Tyr(tBu)-Aib-OH contributes to the design of biomaterials and peptide-based assemblies. Aib-containing sequences are used to produce stable helices that can self-assemble into ordered nanostructures. The presence of protected tyrosine residues enables selective deprotection and further modification, making the dipeptide versatile in the construction of functionalized peptide materials.

The development and use of Boc-Tyr(tBu)-Aib-OH highlight the sophistication of peptide chemistry, where protecting groups and non-proteinogenic amino acids are strategically combined to achieve structural precision and functional control. By serving as a reliable intermediate in synthesis, it has enabled progress in understanding peptide structure and function while also providing pathways to practical applications in drug discovery and materials science.

References

2024. A method for preparing Tirzepatide by solid-liquid combination. Publication Number: CN-118005767-A.
2023. A kind of synthesis method of Boc-Tyr(tBu)-Aib-OH. Publication Number: CN-116715722-A.
2023. Short peptide Boc-L-Tyr(tBu)-Aib-OH and its preparation method. Publication Number: CN-116375792-A.