Fmoc-L-Thr(TBDMS)-OH is an Fmoc-protected amino acid derivative of L-threonine in which the side-chain hydroxyl is capped with a TBDMS (tert-butyldimethylsilyl) silyl protecting group. The molecule contains a free carboxylic acid functionality and an Fmoc carbamate on the amino group, while the threonine side chain bears the sterically protected O-TBDMS ether that modulates polarity and suppresses side reactions from the hydroxyl during coupling chemistry. In synthesis, it is used as a protected building block for stepwise peptide assembly, where the orthogonal protection pattern supports controlled chemoselectivity and the silyl group can be removed under conditions compatible with the Fmoc strategy to reveal the threonine side-chain alcohol for further functionalization or peptide chemistry.
CAT No: CP25363
CAS No:146346-82-9
Synonyms/Alias:Fmoc-Thr(TBDMS)-OH;146346-82-9;Fmoc-O-(tert.-butyldimethylsilyl)-L-threonine;AmbotzFAA1747;FMOC-THR-OH;22670_ALDRICH;22670_FLUKA;MolPort-003-928-149;AKOS016014483;ZINC169748395;AK131094;ST24047304;N-(9H-Fluorene-9-ylmethoxycarbonyl)-O-(tert-butyldimethylsilyl)-L-threonine;(2S,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoicacid
Chemical Name:N-alpha-(9-Fluorenylmethyloxycarbonyl)-O-(t-butyl-dimethylsilyl)-L-threonine
Fmoc-L-Thr(TBDMS)-OH is an Fmoc-protected L-threonine derivative bearing a TBDMS-protected side-chain hydroxyl, providing a stable chiral amino acid building block for peptide chemistry. The molecule contains an N-(9H-fluoren-9-ylmethoxycarbonyl) carbamate that controls amine reactivity during solid-phase or solution-phase coupling, while the C-terminal carboxylic acid remains available for activation and peptide bond formation. The threonine stereocenter is retained as the L-configuration, and the side-chain oxygen is masked as a tert-butyldimethylsilyl ether, reducing hydrogen-bonding and minimizing undesired side reactions during chain assembly. The presence of both a protected hydroxyl and a robust silyl group makes the compound suitable for orthogonal deprotection workflows that can reveal the native threonine functionality at a later stage.
1. Peptide Synthesis
Fmoc-L-Thr(TBDMS)-OH is used as a peptide building block in automated and manual peptide synthesis where controlled N-protection and side-chain masking are required. The Fmoc carbamate supports reliable N-terminal deprotection chemistry that exposes the amino group for successive amide bond formation, while the TBDMS-protected threonine hydroxyl prevents premature O-alkylation, O-acylation, or hydrogen-bond-driven coupling artifacts. The intact L-stereochemistry ensures stereodefined incorporation of threonine into peptide sequences, enabling consistent conformational behavior in downstream peptide analogs. The free carboxylic acid enables standard peptide coupling strategies, and the protected side-chain can be unmasked to generate threonine-containing motifs for biochemical assays and peptide library construction.
2. Side-Chain Functionalization
Fmoc-L-Thr(TBDMS)-OH supports amino acid derivatization and post-synthetic modification strategies targeting threonine side-chain chemistry. The TBDMS ether acts as a protecting group that can be removed under orthogonal conditions to regenerate the primary alcohol functionality on the side chain, enabling subsequent transformations such as ester formation, etherification, or conjugation handle installation. The threonine backbone provides a stereodefined scaffold for constructing functionalized peptidomimetics and for tuning polarity and hydrogen-bonding patterns in structure-activity relationship studies. The Fmoc group and carboxylic acid functionality also allow the compound to be incorporated into protected intermediates, supporting staged synthesis where side-chain activation occurs after peptide assembly or fragment coupling.
3. Peptidomimetics Construction
Fmoc-L-Thr(TBDMS)-OH is applied in peptidomimetic and constrained scaffold synthesis where threonine-derived stereocenters and masked hydroxyl groups are used to manage reactivity. The protected hydroxyl reduces competing reactions during fragment assembly and can be selectively unveiled to introduce oxygen-containing substituents that influence receptor binding or enzymatic recognition patterns. The Fmoc-protected amine and carboxylic acid enable incorporation into longer sequences or into protected oligomer fragments that later undergo functional group interconversions. The resulting threonine-bearing intermediates can serve as precursors for analog generation, including hydroxyl-functional analogs used in synthetic organic chemistry for mapping structure-function relationships.
4. Chemical Biology Research
Fmoc-L-Thr(TBDMS)-OH is utilized in chemical biology workflows requiring threonine-containing probes, enzyme substrates, or modified peptide constructs with controlled functional group exposure. The TBDMS-protected side-chain hydroxyl helps maintain stability during peptide assembly and storage, while later deprotection can generate a defined alcohol handle for conjugation to affinity tags, fluorophores, or biophysical reporters. The L-threonine stereochemistry supports consistent recognition by enzymes and binding domains that discriminate stereochemical and hydrogen-bonding features. The Fmoc-protected amino acid format also integrates into mixed-protection peptide strategies, enabling systematic generation of labeled peptide variants for biochemical investigation and analytical characterization.
5. Pharmaceutical Manufacturing
Fmoc-L-Thr(TBDMS)-OH is relevant to pharmaceutical manufacturing and process chemistry for producing threonine-containing peptide intermediates with robust protection strategies. The Fmoc carbamate and TBDMS side-chain ether provide manufacturing-compatible orthogonal protection, allowing controlled deprotection steps that can be aligned with downstream purification and formulation requirements for peptide-based ingredients or intermediates. The carboxylic acid functionality supports scalable peptide coupling operations, while the masked hydroxyl reduces side reactions that can complicate impurity profiles during synthesis. The stereodefined L-threonine center and protected side-chain facilitate reproducible intermediate generation for route design in fine chemical production where peptide building blocks must withstand multistep processing.
6. Analytical Research
Fmoc-L-Thr(TBDMS)-OH is suitable for analytical research where defined protected amino acid standards and peptide fragments are needed for method development and impurity mapping. The combination of Fmoc and TBDMS protection yields a chemically characterized intermediate that can be incorporated into reference peptides or used as a starting material for generating deprotected threonine-containing controls. The presence of a single stereodefined L-threonine unit supports consistent chromatographic and spectrometric behavior when comparing protected versus deprotected forms. The compound's functional group pattern also enables targeted derivatization routes for LC-MS or HPLC method refinement, supporting reliable monitoring of peptide coupling outcomes and side-chain deprotection events in analytical workflows.
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