Boc-4-Pyridylalanine: Properties, Uses & FAQs

2-((tert-Butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoic acid is a Boc-protected non-natural amino acid bearing a pyridin-4-ylmethyl side chain, widely employed as a building block in solid-phase and solution-phase peptide synthesis and in the design of pyridine-containing bioactive molecules.

Chemical Name

2-((tert-Butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoic acid

Common Synonym

Boc-4-Pyridylalanine; Boc-Pal(4)-OH

SKU

A708626

Molecular Formula

C₁₃H₁₈N₂O₄

Molecular Weight

266.29 g/mol

Functional Class

Boc-protected non-natural amino acid / peptide synthesis building block

Key Structural Feature

α-amino acid with a pyridin-4-ylmethyl side chain and tert-butoxycarbonyl (Boc) N-protecting group

Chemical Identity and Structure

2-((tert-Butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoic acid (Boc-4-Pyridylalanine) is a non-proteinogenic α-amino acid in which the side chain of the parent amino acid 4-pyridylalanine is a pyridin-4-ylmethyl (4-picolyl) group. The α-amino function is protected by a tert-butoxycarbonyl (Boc) group, which renders the compound stable under mildly basic and neutral conditions and readily removable by dilute acid (e.g., trifluoroacetic acid or 4 M HCl in dioxane) without affecting most acid-labile protecting groups used in Fmoc/tBu or Boc/Bzl strategies.

Molecular formula: C₁₃H₁₈N₂O₄; molecular weight: 266.29 g/mol. The molecule contains a stereogenic α-carbon; the enantiopure L- or D-form may be specified upon ordering. The pyridine nitrogen provides an additional coordination or hydrogen-bonding site that is exploited in metal-chelating peptides and structure–activity studies.

Key Physicochemical Properties and Handling

Boc-4-Pyridylalanine is typically a white to off-white crystalline solid at room temperature. As with most Boc-amino acids, it is soluble in polar aprotic solvents such as DMF, DMSO, and acetonitrile, and moderately soluble in ethyl acetate, dichloromethane, and methanol. Aqueous solubility is pH-dependent due to the carboxylic acid and the pyridine nitrogen (pKa values characteristic of pyridinium and carboxylate moieties).

Handle the compound under inert conditions when working with solutions over extended periods to avoid moisture uptake. Weigh in a well-ventilated fume hood using standard laboratory precautions for fine organic powders. Avoid prolonged exposure to strong acids or bases, which can cleave the Boc group or hydrolyze the carboxylate, respectively. Always consult the Safety Data Sheet (SDS) before first use.

Storage Conditions and Stability

Store 2-((tert-Butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoic acid (SKU A708626) in a cool, dry location away from light and moisture. Refrigerated storage at 2–8 °C in a tightly sealed container under an inert atmosphere (nitrogen or argon) is recommended to maximize shelf life. The Boc protecting group is susceptible to acid-catalyzed hydrolysis, so storage away from acidic vapors is important.

If long-term stock solutions are prepared in DMF or DMSO, aliquot and store at –20 °C to minimize freeze-thaw degradation. Check the certificate of analysis (CoA) for lot-specific purity data and expiry information before use. Discard any lot showing discoloration, clumping, or unexpected odor.

Research Applications in Peptide Synthesis and Medicinal Chemistry

Boc-4-Pyridylalanine serves primarily as a building block for the incorporation of a pyridine-containing non-natural residue into peptide sequences. The pyridin-4-yl side chain confers metal-coordination capability (e.g., with Cu²⁺, Zn²⁺, Ni²⁺), making the resulting peptides useful as scaffolds for metalloenzyme inhibitors, metal-chelating biomaterials, and model compounds for bioinorganic chemistry studies.

In medicinal chemistry, replacement of phenylalanine with 4-pyridylalanine introduces a basic nitrogen into the side chain, modulating lipophilicity (logP), pKa, and potential for hydrogen bonding with biological targets. This bioisosteric substitution strategy is employed to optimize absorption, distribution, metabolism, and excretion (ADME) profiles of peptide-derived drug candidates. The compound is compatible with standard Boc-strategy solid-phase peptide synthesis (SPPS) and can also be used in solution-phase coupling with common reagents such as DIC/HOBt, HATU, or HBTU/DIPEA.

Quality, Purity, and Ordering Information

Aladdin Scientific supplies 2-((tert-Butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoic acid under SKU A708626. Purity is confirmed by HPLC and/or NMR analysis; refer to the product page and the lot-specific certificate of analysis (CoA) for exact purity specifications. Research-grade material is suitable for synthetic and biochemical research applications.

For bulk quantities, custom purity grades, or specific enantiomers, contact Aladdin Scientific customer support or submit a bulk inquiry through the website. When ordering, verify that the stereochemistry (L or D) meets your experimental requirements, as the racemic form or individual enantiomers may be offered as distinct catalog items. All orders are subject to Aladdin Scientific's standard terms and conditions.

Frequently asked questions

What is the Boc group in Boc-4-Pyridylalanine, and how is it removed?

The Boc (tert-butoxycarbonyl) group is an acid-labile N-protecting group that shields the α-amino function during synthesis. It is cleanly removed by treatment with a strong acid such as trifluoroacetic acid (TFA, typically 20–50% in DCM) or 4 M HCl in dioxane, generating the free amine as its salt along with isobutylene and CO₂ as gaseous by-products.

Is 2-((tert-Butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoic acid compatible with Fmoc-based SPPS?

The compound carries a Boc N-protecting group rather than Fmoc, so it is primarily designed for Boc-strategy SPPS. However, it can also be incorporated as a single building block in Fmoc-strategy synthesis as a side-chain or backbone coupling partner when the free carboxylic acid is activated, provided the Boc group is subsequently deprotected under acidic conditions that are orthogonal to the Fmoc strategy. Researchers should verify orthogonality with their specific protection scheme before use.

What solvents are recommended for dissolving SKU A708626?

Boc-4-Pyridylalanine (A708626) dissolves well in polar aprotic solvents such as DMF, DMSO, and acetonitrile, and is also soluble in dichloromethane and ethyl acetate. Aqueous solubility is limited at neutral pH but improves under mildly acidic or basic conditions due to ionization of the carboxylic acid and pyridine nitrogen. For stock solution preparation, DMF or DMSO is generally preferred.

Why is a pyridine-containing amino acid useful in drug discovery?

The pyridine ring is a privileged scaffold in medicinal chemistry owing to its ability to engage in hydrogen bonding, π-stacking interactions, and metal coordination with biological targets. Incorporating 4-pyridylalanine into a peptide bioisosterically replaces phenylalanine's aryl side chain with a heteroaromatic ring that is less lipophilic and carries a basic nitrogen, which can improve aqueous solubility and modulate target binding affinity and selectivity.

How should I confirm the purity and identity of the received batch?

Upon receipt, request or download the lot-specific certificate of analysis (CoA) from the Aladdin Scientific website using the lot number printed on the label. The CoA will include purity data (typically HPLC), structural confirmation (¹H NMR or MS), and physical appearance. If additional in-house verification is required, HPLC, LC-MS, or NMR in deuterated DMSO or CDCl₃ are standard analytical approaches for this class of Boc-amino acid.

References

1. Bodanszky, M.; Bodanszky, A. The Practice of Peptide Synthesis, 2nd ed.; Springer: Berlin, 1994. (General reference for Boc-strategy SPPS and amino acid building blocks.)
2. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 4th ed.; Wiley-Interscience: Hoboken, NJ, 2007. (Boc protecting group chemistry and deprotection conditions.)
3. Meanwell, N. A. Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design. J. Med. Chem. 2011, 54, 2529–2591. (Pyridine as bioisostere for phenyl in medicinal chemistry.) doi:10.1021/jm101522v

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.