Boc-3-cyano-D-β-homophenylalanine: Properties & Lab Use Guide

Boc-3-cyano-D-β-homophenylalanine is a non-natural, Boc-protected β-homo amino acid bearing a nitrile substituent on the phenyl ring, widely used as a versatile building block in the solid-phase peptide synthesis and medicinal chemistry research.

Product SKU

B349360

Santa Cruz Reference

sc-293657

Compound Class

Boc-protected non-natural β-homo amino acid

Key Functional Groups

Boc carbamate (N-protecting group), free carboxylic acid, nitrile (cyano) on aryl ring

Stereochemistry

D-configuration β-homo backbone (one additional methylene relative to α-amino acid)

Primary Application

Building block for peptide synthesis and peptidomimetic design

Storage Recommendation

Store at 2–8 °C, away from moisture and light (general guideline for Boc amino acids; verify with CoA)

Chemical Identity and Structural Features

Boc-3-cyano-D-β-homophenylalanine belongs to the class of non-natural β-amino acids in which the backbone is extended by one methylene unit compared with a standard α-amino acid. The D-configuration at the β-carbon provides stereochemical control that is critical for enantioselective applications and for mimicking bioactive conformations not accessible with L-amino acids.

The 3-cyano substituent on the phenyl ring introduces an electron-withdrawing group that can modulate π-system electronics, influence intermolecular interactions with biological targets, and serve as a synthetic handle for further functionalization—for example, via hydrolysis to a carboxamide or carboxylic acid, or via cycloaddition chemistry to access tetrazole or aminomethyl motifs.

The tert-butyloxycarbonyl (Boc) group protects the amine during coupling steps and is cleanly removed under mild acidic conditions (e.g., trifluoroacetic acid/DCM), making this compound fully compatible with standard Boc solid-phase peptide synthesis (SPPS) and solution-phase peptide chemistry workflows.

Research Applications and Use Cases

Peptidomimetic and Foldamer Research: β-Homo amino acids are foundational monomers in the design of β-peptides and mixed α/β-peptide foldamers. Incorporating a D-configured β-homo residue with an electron-deficient aryl side chain enables researchers to probe protease resistance, tune helical propensity, and investigate novel secondary structures including 12-helices and hairpin turns.

Medicinal Chemistry and Drug Discovery: The nitrile group at the 3-position of the phenyl ring is a recognized pharmacophore in many drug scaffolds. This compound can be used to incorporate a metabolically stable, polar aromatic element into peptide-based lead compounds, potentially enhancing target engagement or membrane permeability depending on the design context.

Solid-Phase Peptide Synthesis (SPPS): As a Boc-protected building block with a free carboxylic acid, Boc-3-cyano-D-β-homophenylalanine is directly compatible with standard HBTU, DIC/Oxyma, or PyBOP coupling protocols on Boc-SPPS resins. Researchers should confirm coupling efficiency by Kaiser or chloranil tests due to the potential steric demands of the β-backbone extension.

Bioconjugation and Probe Design: The cyano group can be transformed into additional functionalities post-assembly, enabling modular probe synthesis, affinity labeling, or introduction of isotopic labels for mechanistic studies.

Handling, Storage, and Safety Guidelines

Storage: Boc-protected amino acids are generally hygroscopic and should be stored in a tightly sealed container at 2–8 °C, protected from light and moisture. Users should verify exact storage conditions from the Certificate of Analysis (CoA) supplied with each lot. Allow the container to equilibrate to room temperature before opening to minimize condensation-related degradation.

Handling: Work in a well-ventilated fume hood when weighing or dissolving the compound. Although the nitrile group is relatively stable under ambient conditions, standard laboratory precautions for handling organic compounds containing cyano groups apply—avoid inhalation of dust and contact with strong acids or bases that could hydrolyze the nitrile under forcing conditions. Wear appropriate PPE including nitrile gloves, safety glasses, and a lab coat.

Solubility: Boc-β-amino acids are typically soluble in polar aprotic solvents such as DMF, DMSO, and DCM, and in mixtures thereof. Solubility in aqueous buffers is generally limited and pH-dependent due to the carboxylic acid moiety. Prepare stock solutions fresh or store aliquots at −20 °C under inert atmosphere to prevent ester or amide bond formation.

Disposal: Dispose of waste in accordance with local institutional and regulatory guidelines for organic chemical waste. Do not pour solutions containing nitrile compounds directly down the drain without appropriate treatment.

Quality, Purity, and Ordering Information

Boc-3-cyano-D-β-homophenylalanine is available from Aladdin Scientific under SKU B349360. This product is also cross-referenced to Santa Cruz catalog number sc-293657, facilitating straightforward literature and supplier cross-referencing for procurement teams.

Each lot is accompanied by a Certificate of Analysis (CoA) documenting purity (typically assessed by HPLC), identity confirmation (NMR and/or MS), and specific optical rotation where applicable. Researchers should request the CoA for the specific lot number received to confirm that purity meets the requirements of their application—SPPS typically demands ≥95% purity to minimize deletion sequences and racemization artifacts.

For custom quantities, bulk orders, or requests for additional analytical data (e.g., chiral HPLC, elemental analysis), contact Aladdin Scientific technical support or your regional sales representative. Volume pricing may be available for larger quantities.

Frequently asked questions

What coupling reagents are recommended for incorporating Boc-3-cyano-D-β-homophenylalanine into a peptide sequence?

Standard amide-bond coupling reagents such as HBTU/HOBt, DIC/Oxyma Pure, or PyBOP in DMF or NMP are generally suitable. Due to the steric bulk introduced by the β-backbone extension, extended coupling times or double-coupling protocols may be necessary. Monitor coupling completeness by Kaiser or chloranil test.

How should the Boc protecting group be removed from this compound after coupling?

The Boc group is removed under standard acidic conditions, most commonly using 20–50% trifluoroacetic acid (TFA) in dichloromethane (DCM) for 20–30 minutes at room temperature, or by treatment with 4 M HCl in dioxane. The cyano group on the phenyl ring is stable to these deprotection conditions and is not affected.

Can the cyano group on this compound be further functionalized after peptide assembly?

Yes. The nitrile group is a versatile synthetic handle that can be converted to a carboxamide (partial hydrolysis), carboxylic acid (full hydrolysis), tetrazole (via [3+2] cycloaddition with azide), or aminomethyl group (via reduction). These transformations allow post-assembly diversification of peptide-based libraries.

Why use a D-configured β-homo amino acid rather than an L-configured one?

D-configured residues impart different helical sense and turn geometry in β-peptide foldamers compared to L-residues, enabling access to distinct secondary structures. Additionally, D-amino acids confer resistance to proteolytic degradation by most mammalian proteases, which is advantageous in peptide-based drug design.

What solvents are appropriate for preparing stock solutions of this compound?

DMF and DMSO are the most commonly used solvents for Boc-protected β-amino acids and typically provide good solubility. DCM is also suitable for short-term use. Aqueous solubility is limited; if aqueous solutions are required, small amounts of base (e.g., NaOH or NH4OH) may assist dissolution by deprotonating the carboxylic acid. Always verify compatibility with downstream assay conditions.

References

1. Seebach, D.; Gardiner, J. β-Peptidic Peptidomimetics. Accounts of Chemical Research, 2008, 41(10), 1366–1375. doi:10.1021/ar700263g
2. Cheng, R. P.; Gellman, S. H.; DeGrado, W. F. β-Peptides: From Structure to Function. Chemical Reviews, 2001, 101(10), 3219–3232. doi:10.1021/cr000045i
3. Aladdin Scientific Product Page: Boc-3-cyano-D-β-homophenylalanine, SKU B349360. Aladdin Scientific.

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