O-Benzyl-N-(Boc)-L-Homoserine: Properties & Lab Uses
O-Benzyl-N-(Boc)-L-Homoserine: Properties & Lab Uses
O-Benzyl-N-(tert-butoxycarbonyl)-L-homoserine is a dual-protected, enantiomerically pure L-homoserine derivative widely used as a building block in Boc-strategy solid-phase and solution-phase peptide synthesis.
- Chemical Name
- O-Benzyl-N-(tert-butoxycarbonyl)-L-homoserine
- SKU
- B185445
- Protecting Groups Present
- Boc on α-amine; benzyl ether on γ-hydroxyl
- Stereochemistry
- L-configuration (S) at α-carbon
- Key Application
- Building block for Boc solid-phase and solution-phase peptide synthesis
- Boc Removal Condition
- Trifluoroacetic acid (TFA) or anhydrous HCl in dioxane
- Benzyl Removal Condition
- Hydrogenolysis (H₂/Pd-C) under standard conditions
What Is O-Benzyl-N-(Boc)-L-Homoserine?
O-Benzyl-N-(tert-butoxycarbonyl)-L-homoserine is a protected, non-proteinogenic amino acid derivative of L-homoserine. L-Homoserine itself is a naturally occurring amino acid that serves as a biosynthetic intermediate in the aspartate family pathway. In its protected form (SKU B185445), two orthogonal protecting groups are installed: a tert-butoxycarbonyl (Boc) group shields the α-amino function, while a benzyl (Bn) ether protects the side-chain γ-hydroxyl group. The free carboxylic acid remains available for coupling reactions. This orthogonal protection scheme allows selective, stepwise removal of each protecting group under different conditions, making the compound exceptionally versatile in multi-step synthesis.
The compound retains the L (S) absolute configuration at the α-carbon, ensuring stereochemical integrity is preserved when incorporated into target peptides or peptidomimetics.
Physical, Chemical, and Storage Properties
O-Benzyl-N-(Boc)-L-homoserine is typically obtained as a white to off-white crystalline solid. The compound contains a free carboxylic acid (pKa characteristic of α-amino acids), a Boc-protected amine, and a benzyl-protected hydroxyl, giving it moderate polarity. It is generally soluble in common organic solvents such as dichloromethane, ethyl acetate, dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), and shows limited solubility in water.
Storage recommendations: Store the compound in a tightly sealed container at 2–8 °C, protected from moisture and light, to prevent hydrolysis of the acid-labile Boc group and to maintain optical purity. Under these conditions the material is expected to remain stable for an extended shelf life. Always allow the container to equilibrate to room temperature before opening to prevent condensation-driven degradation.
Handling precautions: Follow standard laboratory safety practices. Consult the Safety Data Sheet (SDS) before use. Avoid inhalation of dust and contact with skin or eyes. Work in a well-ventilated area or fume hood.
Deprotection Strategies and Synthetic Applications
Boc removal: The Boc group is selectively removed under mild acidic conditions. Treatment with trifluoroacetic acid (TFA) in dichloromethane (typically 20–50% v/v) at room temperature for 15–30 minutes is the standard protocol. Alternatively, anhydrous HCl in 1,4-dioxane may be used. These conditions leave the benzyl ether intact, exposing the free α-amine for the next coupling cycle in Boc-strategy solid-phase peptide synthesis (SPPS).
Benzyl removal: The O-benzyl ether is cleaved by hydrogenolysis using H₂ gas over palladium on carbon (Pd/C) in a protic solvent such as methanol or ethanol at atmospheric pressure. This orthogonal step selectively deprotects the hydroxyl without disturbing other functional groups that are stable to hydrogenolysis. Alternatively, the benzyl group is removed during the final HF cleavage step in classical Boc/Bzl SPPS.
Synthetic utility: As a building block, this compound enables the incorporation of L-homoserine residues into peptides, cyclic peptides, peptidomimetics, and natural product analogues. The free carboxylic acid can be activated as an N-hydroxysuccinimide (NHS) ester, mixed anhydride, or other activated ester for solution-phase coupling. It is also employed in the synthesis of homoserine lactone precursors and in the preparation of modified peptides for structure–activity relationship (SAR) studies.
Quality, Purity, and Ordering Information
Purity: Aladdin Scientific supplies O-Benzyl-N-(Boc)-L-homoserine (SKU B185445) with a defined purity specification. Customers should consult the product page or Certificate of Analysis (CoA) for the current lot-specific purity value, determined by methods such as HPLC and/or NMR. Optical purity (enantiomeric excess, ee) is a critical parameter for stereoselective synthesis; the CoA should be reviewed for the ee value of each lot.
Available formats: The compound is available in research quantities. Please visit the Aladdin Scientific product page for current pack sizes, pricing, and stock availability.
Ordering: Order directly through the Aladdin Scientific website using SKU B185445. For bulk inquiries, custom synthesis requirements, or institutional procurement, contact Aladdin Scientific customer support. For regulatory and compliance documentation (SDS, CoA), download directly from the product page or request from your sales representative.
Frequently asked questions
What protecting groups are present in O-Benzyl-N-(Boc)-L-homoserine and are they orthogonal?
Yes, the two protecting groups are orthogonal. The Boc group on the α-amine is removed by mild acid (TFA or HCl/dioxane), while the O-benzyl ether on the γ-hydroxyl is removed by hydrogenolysis (H₂/Pd-C) or HF. Because each group requires a chemically distinct deprotection condition, they can be removed independently and in any desired sequence without affecting the other.
Is the L-stereochemistry at the α-carbon preserved during standard Boc deprotection?
Yes. Standard Boc removal with TFA in DCM or HCl in dioxane proceeds under mild conditions that do not affect the stereocenter at the α-carbon. Racemization is not expected during this step. However, researchers should confirm optical purity by chiral HPLC or polarimetry if the synthetic application is sensitive to epimerization.
How should O-Benzyl-N-(Boc)-L-homoserine be stored to maintain stability?
Store the compound in a tightly sealed container at 2–8 °C, away from moisture and light. The Boc group is susceptible to hydrolysis under acidic or humid conditions, so a dry, cool environment is essential. Allow the container to warm to room temperature before opening to avoid moisture condensation on the product.
Can this compound be used as a building block in Fmoc-strategy SPPS?
O-Benzyl-N-(Boc)-L-homoserine is primarily designed for Boc-strategy SPPS, where the Boc group serves as the temporary α-amine protectant and the benzyl ether acts as a semi-permanent side-chain protecting group removed during final HF cleavage. For Fmoc-strategy SPPS, an Fmoc-protected homoserine derivative with an acid-stable (e.g., tert-butyl) side-chain protecting group is typically preferred, as the standard Fmoc piperidine deprotection cycle is incompatible with TFA-sensitive protecting groups used in alternating Boc/Fmoc schemes.
What solvents are recommended for dissolving O-Benzyl-N-(Boc)-L-homoserine in peptide coupling reactions?
The compound is generally soluble in polar aprotic solvents such as DMF, DMSO, and DCM, which are standard solvents for peptide coupling. Ethyl acetate and THF are also suitable for certain coupling procedures. Aqueous solubility is limited due to the hydrophobic Boc and benzyl groups, so aqueous-based coupling systems are not recommended without co-solvent optimization.
References
- Bodanszky, M. & Bodanszky, A. The Practice of Peptide Synthesis, 2nd ed. Springer, Berlin, 1994.
- Merrifield, R. B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 1963, 85, 2149–2154. doi:10.1021/ja00897a025
- Greene, T. W. & Wuts, P. G. M. Protective Groups in Organic Synthesis, 4th ed. Wiley-Interscience, New York, 2007.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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