DL-Cyclobutylglycine is a free amino acid derivative classified as a cycloalkyl-substituted glycine analogue, featuring an amino acid backbone bearing a cyclobutyl side chain instead of the hydrogen side chain of glycine. The molecule contains both an amino group and a carboxyl group on the α-carbon framework, and its DL designation indicates a racemic mixture of stereoisomers at the chiral center. DL-Cyclobutylglycine is used in peptide chemistry and structure-activity studies as a non-proteinogenic residue precursor to introduce a conformationally constrained cyclobutyl side chain into synthetic peptides or related amino acid derivatives.
CAT No: CP20903
DL-Cyclobutylglycine is a nonproteinogenic amino acid bearing a cyclobutyl side chain attached to the alpha carbon, with a chiral center present in the glycine-like backbone and a carboxylic acid and primary amine functionality. The DL designation indicates a racemic mixture of stereoisomers, which is often selected when stereochemical resolution is not yet required or when downstream steps can tolerate racemization. The cyclobutyl group introduces a compact, conformationally constrained hydrophobic motif that can influence peptide secondary structure propensity and binding-site shape complementarity. The amino acid's reactive amine and acid groups support standard protection and coupling strategies, making it suitable as a chiral precursor, peptide building block precursor, or derivatization intermediate in synthetic organic chemistry.
1. Peptide Synthesis
DL-Cyclobutylglycine is applied in peptide synthesis as a side-chain modified amino acid for constructing cyclobutyl-containing peptide bonds under standard coupling chemistries. The amino acid's carboxyl group and primary amine enable conversion into protected amino acid derivatives for sequential N-to-C assembly, while the cyclobutyl side chain can be retained through typical protecting-group cycles. Racemic incorporation can be used for generating libraries of conformationally constrained analogs, followed by later stereochemical separation if enantioselective behavior becomes a key variable. Downstream peptide products can serve as intermediates for peptidomimetic scaffolds, protease-substrate probes, or structure-activity relationship studies where hydrophobic packing and backbone restriction are probed.
2. Chiral Building Block Development
DL-Cyclobutylglycine is suitable for chiral synthesis workflows where the cyclobutylglycine motif is needed as a starting point for enantiopure material preparation. The stereogenic alpha carbon allows conversion into protected amino acid intermediates, enabling resolution strategies such as diastereomeric salt formation or chiral auxiliary-based separation at the protected stage. The resulting enantiomerically enriched protected amino acid can then be used for stereodefined peptide coupling, minimizing stereochemical ambiguity in downstream analog construction. This makes DL-Cyclobutylglycine a practical precursor in chiral amino acid chemistry and method development for stereocontrolled synthesis of constrained amino acid derivatives.
3. Side-Chain Functionalization
DL-Cyclobutylglycine is used in amino acid derivatization programs targeting side-chain and backbone modifications that preserve the cyclobutyl hydrophobic core. The primary amine can be protected for selective transformations, while the carboxylic acid can be activated or esterified to enable controlled intermediate formation for later functional group installation. Cyclobutylglycine derivatives can be further elaborated into functionalized peptidomimetic fragments, including handles for conjugation, scaffolding units for medicinal chemistry, or intermediates for building constrained analogs with altered polarity and steric profiles. Downstream products can feed into combinatorial synthesis and SAR studies by providing a consistent conformational motif across a series of analogs.
4. Chemical Biology Probes
DL-Cyclobutylglycine is applied in chemical biology research to generate constrained amino acid-containing peptides and peptidomimetics used for probing binding-site geometry and conformational effects. The amino acid's protected N- and C-reactive sites support incorporation into peptide probes, while the cyclobutyl side chain can function as a hydrophobic, shape-defining element that perturbs local structure. Racemic material can support initial screening of analog classes, with stereochemical refinement performed when structure-dependent recognition is indicated by binding or reactivity trends. The resulting probe molecules can serve as biochemical research intermediates for studying receptor-ligand interactions, enzyme tolerance to nonproteinogenic residues, and structure-function relationships in molecular recognition.
5. Pharmaceutical Intermediate Preparation
DL-Cyclobutylglycine is relevant to pharmaceutical intermediate preparation where nonproteinogenic amino acid motifs are incorporated into drug-like peptidomimetics and constrained analogs. The amino acid's carboxyl and amine groups enable conversion into protected building blocks compatible with peptide coupling and subsequent deprotection steps in synthetic sequences. The cyclobutyl side chain can support medicinal chemistry optimization by modulating hydrophobic surface area and conformational preferences, which can be important for downstream scaffold diversification. Industrially, this compound can function as a process chemistry intermediate for fine chemical synthesis routes that require amino acid-based inputs for controlled assembly of complex molecules.
6. Process Chemistry And Fine Chemical Synthesis
DL-Cyclobutylglycine is employed in process chemistry and fine chemical synthesis as a readily handled amino acid feedstock for producing protected amino acid derivatives and downstream coupling-ready intermediates. The presence of a stable amino acid backbone supports scalable protection strategies and activation of the carboxyl group to form esters or activated acids suitable for controlled manufacturing steps. Racemic sourcing can simplify early-stage production logistics, with later stereochemical control introduced through resolution or enantioselective downstream processing when required by the target specification. The cyclobutylglycine motif thereby serves as a manufacturable chiral amino acid precursor class for producing constrained building blocks used in peptide science, peptidomimetic construction, and industrial synthesis of amino acid-derived specialty chemicals.
1. SERS spectrum of the peptide thymosin‐β4 obtained with Ag nanorod substrate
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