(S)-Boc-O-Ethylserine: Properties, Uses & FAQs

(S)-2-((tert-Butoxycarbonyl)amino)-3-ethoxypropanoic acid is a Boc-protected, O-ethylated L-serine derivative widely used as a non-natural amino acid building block in solid-phase and solution-phase peptide synthesis.

IUPAC Name

(S)-2-((tert-Butoxycarbonyl)amino)-3-ethoxypropanoic acid

SKU

A728215

Stereochemistry

S-configuration at the alpha carbon (L-amino acid series)

Protecting Group

tert-Butoxycarbonyl (Boc) on the alpha-amine; ethyl ether on the side-chain hydroxyl

Functional Class

Non-natural Boc-amino acid / O-alkylated serine derivative

Primary Application

Building block for peptide synthesis and medicinal chemistry

Supplier

Aladdin Scientific (aladdin-e.com)

What Is (S)-2-((tert-Butoxycarbonyl)amino)-3-ethoxypropanoic Acid?

(S)-2-((tert-Butoxycarbonyl)amino)-3-ethoxypropanoic acid, commonly abbreviated as Boc-O-Et-Ser-OH or Boc-O-ethyl-L-serine, is a synthetic non-natural amino acid derivative. It belongs to the broad family of Boc-protected alpha-amino acids in which the alpha-amine is shielded by a tert-butoxycarbonyl (Boc) group, and the serine side-chain hydroxyl is permanently alkylated with an ethyl group.

The compound retains a free carboxylic acid, making it directly activatable for amide-bond formation via standard coupling reagents (e.g., HATU, DIC/HOBt, EDCI) in both solid-phase peptide synthesis (SPPS) and solution-phase synthesis. The O-ethyl modification renders the side chain metabolically more stable and more lipophilic than native serine, which is exploited in peptidomimetic and medicinal chemistry programs.

Key Chemical Properties and Handling Considerations

Stability of the Boc group: The Boc carbamate is labile under acidic conditions and is cleanly removed by trifluoroacetic acid (TFA, 20–50% in DCM) or 4 M HCl in dioxane at room temperature, liberating the free amine salt. It is stable to bases, nucleophiles and most oxidants under mild conditions.

Side-chain stability: The O-ethyl ether is stable under both acidic Boc-deprotection conditions and standard basic Fmoc SPPS wash conditions, meaning the ethyl group is not cleaved during routine deprotection steps. This distinguishes it from Fmoc-Ser(tBu)-OH, where the tBu ether is acid-labile.

Solubility: The compound is typically soluble in common organic solvents including DMF, DMSO, DCM, EtOAc and THF. Aqueous solubility is limited at neutral pH but increases under mildly basic conditions due to carboxylate formation.

Storage: Store in a cool, dry place away from light and moisture. Refrigeration (2–8 °C) in a tightly sealed container under inert atmosphere is recommended for long-term storage to prevent hydrolysis or racemization.

Applications in Peptide Synthesis and Medicinal Chemistry

Peptidomimetics and drug discovery: Incorporation of O-ethylserine into peptide sequences is a well-established strategy to improve proteolytic resistance and modulate pharmacokinetic properties. The ethyl side chain mimics the serine hydroxymethyl unit sterically while eliminating the hydrogen-bond donor, which can dramatically alter binding kinetics to target proteins.

SPPS compatibility: Boc-O-Et-Ser-OH is compatible with Boc-strategy SPPS using HF cleavage at the end of synthesis. Because the O-ethyl ether is acid-stable, no side-chain protection conflict arises. It can also be used in Fmoc-strategy synthesis if the Boc group is first converted to Fmoc, or if it is introduced as a C-terminal or fragment-coupling building block.

Fragment condensation and solution synthesis: The free carboxylic acid is readily activated with DIC, HATU, EDCI or PyBOP in the presence of a base (DIPEA or NMM) to form active esters or acylium equivalents for amide coupling in solution phase.

Ordering, Purity and Quality Assurance

Aladdin Scientific offers (S)-2-((tert-Butoxycarbonyl)amino)-3-ethoxypropanoic acid under SKU A728215. Researchers should confirm the purity specification on the current Certificate of Analysis (CoA) at time of purchase, as lot-specific data for optical purity (e.g., enantiomeric excess determined by chiral HPLC) and chemical purity (HPLC area%) are provided on the CoA.

For bulk or custom quantities, please contact the Aladdin Scientific sales team. Pricing, availability and lead times are listed on the product page at aladdin-e.com and are subject to change.

All products are subject to Aladdin Scientific's standard quality-control procedures. If a product does not meet the stated specification, please refer to the Returns and Refunds policy on the website.

Frequently asked questions

What is the difference between (S)-2-((tert-Butoxycarbonyl)amino)-3-ethoxypropanoic acid and standard Boc-L-serine?

The key difference is the side chain: standard Boc-L-serine has a free hydroxyl (-OH) on the beta carbon, whereas this compound has an O-ethyl ether (-OEt). The ethyl modification makes the side chain non-ionizable, more lipophilic, and fully stable to the acidic conditions used for Boc removal, eliminating the need for a separate side-chain protecting group during Boc-strategy SPPS.

How should the Boc group be removed from this compound or from a peptide containing it?

The Boc group is most commonly removed with 20–50% trifluoroacetic acid (TFA) in dichloromethane (DCM) for 15–30 minutes at room temperature, or with 4 M HCl in 1,4-dioxane. Both protocols afford the free alpha-amine as its TFA or HCl salt. The O-ethyl ether on the side chain remains intact under these conditions.

Is this compound compatible with Fmoc solid-phase peptide synthesis?

This compound carries a Boc (not Fmoc) amine protecting group, so it is designed primarily for Boc-strategy SPPS or solution-phase synthesis. However, it can be incorporated into Fmoc SPPS workflows as a C-terminal building block, via fragment condensation, or after manual Boc-to-Fmoc exchange. Users intending to use Fmoc SPPS should verify compatibility with their specific resin and coupling conditions.

What solvents are recommended for dissolving this compound in the lab?

The compound dissolves readily in polar aprotic solvents such as DMF and DMSO, as well as in DCM, EtOAc, and THF. For aqueous applications, dissolution under mildly basic conditions (e.g., dilute NaHCO3 or NaOH solution) is recommended to deprotonate the carboxylic acid and improve water solubility. Avoid prolonged storage of dissolved solutions to minimize hydrolysis risk.

How should I store (S)-2-((tert-Butoxycarbonyl)amino)-3-ethoxypropanoic acid to maintain its integrity?

Store the compound at 2–8 °C in a tightly sealed container under an inert atmosphere (nitrogen or argon) in a cool, dry location away from light. Under these conditions the compound is expected to be stable for an extended period. Always check the lot-specific expiry date on the Certificate of Analysis (CoA) supplied with the product.

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. Carpino, L. A. et al. Boc-amino acid and protecting group stability — textbook-level reference; specific article details require verification.
3. Aladdin Scientific product page for A728215: (S)-2-((tert-Butoxycarbonyl)amino)-3-ethoxypropanoic acid. aladdin-e.com (accessed 2024).

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