DL-Cyclobutylalanine is a non-natural, aliphatic amino acid derivative featuring a cyclobutyl side chain attached to the alpha carbon, with the amino acid backbone bearing an amino group and a carboxyl group. The "DL" designation indicates a racemic mixture of stereoisomers at the alpha stereocenter, and the molecule contains the typical amino acid functional motif suitable for salt formation or conversion to protected or activated forms for peptide chemistry. In research and synthesis, it is used as a cyclobutyl-containing building block to probe structure-property relationships in peptide analogues, to introduce conformationally constrained hydrophobic character into amino acid sequences, or to support chemical labeling and analytical studies requiring a defined non-proteinogenic side chain.
CAT No: CP20803
DL-Cyclobutylalanine is a non-proteinogenic amino acid characterized by an aliphatic cyclobutyl side chain attached to the α-amino acid backbone, providing a compact, conformationally constrained hydrophobic group. The molecule contains an amino functionality and a carboxylic acid group (or, depending on the supplied form, a corresponding protected or derivatized variant), enabling standard amino acid coupling chemistry and downstream functional transformations. The DL designation indicates a racemic mixture at the α-carbon, which supports stereochemical studies and racemate-to-enantiomer workflows when paired with resolution or asymmetric synthesis strategies. The cyclobutyl side chain can influence conformational preference in peptide contexts and can serve as a handle for derivatization into more reactive or analytically informative intermediates.
1. Peptide Synthesis
DL-Cyclobutylalanine supports peptide building-block preparation for solid-phase or solution-phase peptide assembly where a conformationally restricted hydrophobic residue is desired. The amino acid backbone participates in amide bond formation via standard coupling approaches after appropriate N-protection and C-terminal activation, while the cyclobutyl side chain remains stable under typical peptide coupling and deprotection conditions. Racemic incorporation enables rapid generation of peptide libraries for structure-activity relationship studies, including conformational probing where stereochemistry can be treated as a variable. The resulting cyclobutyl-containing peptides can be used to assess backbone and side-chain packing effects and to generate analogs for peptidomimetic construction.
2. Amino Acid Derivatization
DL-Cyclobutylalanine can be converted into amino acid esters, amides, or activated carboxylic acid derivatives to support synthetic organic chemistry and intermediate preparation. The carboxylate functionality enables formation of acylating agents, while the amino group can be protected to control chemoselectivity during multi-step sequences. The cyclobutyl side chain can be retained to maintain steric and conformational characteristics, or it can be used as a scaffold for further functional group installation through side-chain-compatible transformations. Derivatized forms can serve as biochemical research intermediates, chiral building blocks precursors, or feedstocks for generating labeled or tagged analogs used in analytical method development.
3. Chiral Resolution Studies
DL-Cyclobutylalanine is well suited for stereochemical investigations because the racemate can be subjected to resolution strategies that yield enantiopure cyclobutylalanine derivatives. The α-chiral center adjacent to the amine and carboxyl group enables formation of diastereomeric salts or derivatives with chiral auxiliaries, which can be leveraged to separate enantiomers for stereochemically defined peptide synthesis. The cyclobutyl side chain provides a hydrophobic motif that remains consistent across enantiomers, allowing direct comparison of stereochemical effects in downstream peptide analogs. Enantiopure material obtained from DL starting feedstock can then be used to prepare defined N-protected amino acids for controlled incorporation into peptides and peptidomimetics.
4. SAR Peptidomimetics
DL-Cyclobutylalanine can be incorporated into peptidomimetic scaffolds to probe how constrained hydrophobic side chains affect molecular recognition and conformational behavior. The amino acid backbone allows systematic substitution at a specific residue position, while the cyclobutyl group can modulate local steric bulk and hydrophobic surface characteristics relevant to receptor or binding-site interactions in SAR studies. Racemic incorporation can support early-stage library synthesis, with subsequent refinement using enantiopure analogs when stereochemical dependence is observed. Cyclobutyl-containing analogs generated from DL-Cyclobutylalanine can be used to build structure-activity relationship datasets and to guide medicinal chemistry optimization of peptide-like structures.
5. Pharmaceutical Intermediate Preparation
DL-Cyclobutylalanine can function as a process-oriented intermediate for manufacturing routes that require non-proteinogenic amino acid residues. The presence of both amine and carboxylic acid functionalities enables conversion into N-protected amino acid derivatives and activated C-terminal forms that are compatible with peptide coupling steps used in fine chemical production. The cyclobutyl side chain contributes a stable, hydrophobic motif that can be carried through synthetic sequences to produce drug-relevant intermediates such as protected amino acids, peptide fragments, and specialized building blocks for medicinal chemistry programs. Downstream processing can include controlled deprotection to expose reactive functional groups for further assembly, supporting scalable synthesis planning for amino acid-derived intermediates.
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