N-Boc-L-Phenylalaninal: Properties, Uses & Handling FAQ

N-Boc-L-phenylalaninal is a Boc-protected L-phenylalanine-derived α-amino aldehyde widely used as a chiral building block in asymmetric synthesis, peptide chemistry, and the preparation of protease inhibitor scaffolds.

Chemical Name

tert-Butyl ((S)-1-formyl-2-phenylethyl)carbamate (N-Boc-L-phenylalaninal)

CAS Number

To be confirmed — see product datasheet (review flag applied)

Molecular Formula

C₁₂H₁₇NO₃

Molecular Weight

223.27 g/mol

Key Functional Groups

Aldehyde (–CHO), Boc carbamate (N-protecting group), benzyl side chain

Stereochemistry

(S)-configuration at the α-carbon, derived from L-phenylalanine

Recommended Storage

Store at 2–8 °C, protected from light, under inert atmosphere (review flag applied)

What Is N-Boc-L-Phenylalaninal and Why Is It Important?

N-Boc-L-phenylalaninal (Boc-L-Phe-al) is an α-amino aldehyde in which the amino group of L-phenylalanine is protected by a tert-butyloxycarbonyl (Boc) group and the carboxyl terminus has been reduced to an aldehyde. This dual functionality—a reactive electrophilic aldehyde combined with an orthogonally removable nitrogen-protecting group—makes it a versatile chiral synthon.

The compound retains the (S)-stereocentre of the parent amino acid, providing a pre-set chiral centre that can be transferred to target molecules with high fidelity. It is therefore a preferred starting material for the construction of statine-type units, amino alcohols, α-amino acids with extended side chains, and heterocyclic scaffolds of medicinal relevance.

Key Applications in Organic and Medicinal Chemistry

Asymmetric synthesis: The aldehyde carbonyl undergoes highly stereoselective additions (Grignard, Wittig, allylation, reductive amination) under chelation or Felkin–Anh control, leveraging the existing α-stereocentre to set additional chiral centres in one step.

Protease inhibitor synthesis: Boc-L-Phe-al serves as a core electrophilic warhead or precursor in the synthesis of aldehyde-based cysteine and serine protease inhibitors, as well as transition-state analogue inhibitors of aspartyl proteases.

Peptide isostere chemistry: Reductive amination and subsequent functional-group manipulations convert the compound into reduced peptide bond surrogates (ψ[CH₂NH] isosteres), which are incorporated into peptidomimetics to improve metabolic stability.

Heterocycle formation: Condensation reactions of the aldehyde with binucleophiles give access to oxazolines, imidazolines, and other pharmacophoric rings while preserving the Boc group for downstream deprotection.

Handling, Storage, and Stability Considerations

Sensitivity: α-Amino aldehydes are prone to epimerisation at the α-carbon under both acidic and basic conditions, and to self-condensation (aldol-type) reactions. Solutions should be prepared freshly and used promptly. Avoid prolonged exposure to moisture, which can promote hydrate formation and racemisation.

Storage: Keep the compound refrigerated (2–8 °C is a typical recommendation for similar amino aldehydes) in a tightly sealed container under an inert gas (nitrogen or argon). Protect from light. Long-term storage at −20 °C may be advisable to maximise shelf life.

Personal protective equipment: Handle in a well-ventilated fume hood. Wear appropriate gloves, eye protection, and a lab coat. Consult the Safety Data Sheet (SDS) supplied with the product for full hazard information before use.

Epimerisation risk: When using in reactions, maintain mild pH conditions and low temperatures where possible. Monitor enantiomeric excess (ee) by chiral HPLC or optical rotation if stereochemical integrity is critical.

Analytical Characterisation and Purity Assessment

Purity verification: For synthetic applications requiring high stereochemical fidelity, confirm purity by HPLC (reverse-phase C18 or chiral stationary phase) before use. The Aladdin product specification sheet provides the guaranteed purity level; always cross-check the Certificate of Analysis (CoA) supplied with each lot.

Identity confirmation: ¹H NMR should display a characteristic aldehyde proton singlet at approximately δ 9.5–9.7 ppm, Boc methyl signals near δ 1.4 ppm (9H, s), and aromatic protons of the benzyl group in the δ 7.2–7.4 ppm region. Mass spectrometry (ESI-MS or APCI-MS) can confirm the molecular ion or [M+Na]⁺ adduct.

Optical rotation: Measurement of specific optical rotation [α]D²⁰ in a suitable solvent (e.g., CHCl₃ or MeOH) provides a rapid check of enantiomeric integrity. Literature values should be consulted and compared; flag significant deviations for investigation.

Ordering, Specifications, and Quality Assurance

Available from Aladdin Scientific: N-Boc-L-phenylalaninal is listed under SKU B102427. Contact your regional Aladdin representative or visit the product page for current pack sizes, pricing, and availability.

Documentation: Each shipment is accompanied by a Certificate of Analysis (CoA) detailing lot-specific purity, appearance, and analytical data. Safety Data Sheets (SDS) are available for download from the Aladdin website.

Custom quantities: If standard pack sizes do not meet your project requirements, enquire about custom bulk quantities through the Aladdin customer service team.

Quality commitment: Aladdin Scientific applies rigorous quality-control testing to its reagents. If you have concerns about product performance, contact technical support with your lot number and CoA for prompt assistance.

Frequently asked questions

What is the difference between N-Boc-L-phenylalaninal and N-Boc-L-phenylalanine?

N-Boc-L-phenylalanine retains the free carboxylic acid at the C-terminus and is a standard Boc-protected amino acid used directly in solid-phase or solution-phase peptide coupling. N-Boc-L-phenylalaninal, by contrast, has the carboxyl group reduced to an aldehyde (–CHO), making it an electrophilic α-amino aldehyde. This aldehyde functionality enables reactions not available to the carboxylic acid, including nucleophilic additions, reductive aminations, and condensations used to build peptidomimetics and protease inhibitor warheads.

How should I minimise epimerisation when using N-Boc-L-phenylalaninal in a reaction?

To minimise epimerisation, keep reaction temperatures as low as practicable (0 °C or below for sensitive steps), use mildly buffered or neutral conditions, and avoid prolonged reaction times. Prepare solutions of the aldehyde freshly and keep exposure to protic solvents brief. After the reaction, verify stereochemical outcome by chiral HPLC or by measuring specific optical rotation and comparing against the literature value for the expected product.

Can N-Boc-L-phenylalaninal be used directly in solid-phase peptide synthesis (SPPS)?

N-Boc-L-phenylalaninal is not typically used as a standard coupling building block in SPPS because it lacks a carboxylic acid for amide bond formation. Instead, it functions as a solution-phase chiral synthon for the preparation of reduced-amide isostere fragments or peptidomimetic intermediates that are subsequently incorporated into a larger synthetic sequence. If your goal is introduction of a reduced peptide bond (ψ[CH₂NH]) at a phenylalanine position, the aldehyde is reductively aminated onto a resin-bound amine off-resin or on-resin under appropriate conditions.

What solvents are recommended for dissolving N-Boc-L-phenylalaninal?

N-Boc-L-phenylalaninal is generally soluble in common organic solvents such as dichloromethane (DCM), tetrahydrofuran (THF), ethyl acetate, and dimethylformamide (DMF). Avoid prolonged exposure to protic solvents such as water or methanol, as these can promote hydrate formation and racemisation of the aldehyde. Always check solubility empirically with your specific lot, and consult the product CoA or SDS for any additional guidance.

Is N-Boc-L-phenylalaninal suitable for large-scale synthesis?

N-Boc-L-phenylalaninal can be used at larger scales, but the inherent reactivity of the aldehyde—including susceptibility to epimerisation, self-condensation, and oxidation—requires careful process control as scale increases. Rigorous exclusion of moisture and oxygen, temperature control, and in-process analytical monitoring (chiral HPLC, optical rotation) become increasingly important at scale. Contact the Aladdin Scientific team to discuss bulk availability and any technical considerations for your specific application.

References

1. Fehrentz, J.-A.; Castro, B. An efficient synthesis of optically active α-(t-butoxycarbonylamino)aldehydes from α-amino acids. Synthesis 1983, 676–678. (Seminal route to Boc amino aldehydes — verify applicability to this compound)
2. Luly, J. R. et al. Synthesis of peptidyl alpha-keto amides, alpha-keto esters and alpha-diketones and their use as inhibitors of human renin. J. Org. Chem. 1987. (Example use of amino aldehydes in protease inhibitor synthesis — verify citation details)
3. Juaristi, E.; Quintana, D. Enantioselective synthesis using amino acid-derived chiral auxiliaries and building blocks. Tetrahedron: Asymmetry, 1992. (General reference for amino acid-derived aldehyde synthons — verify citation details)

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