L-Cyclobutylglycine is a naturally occurring amino acid derivative in the glycine family where the side chain is substituted with a cyclobutyl group, yielding a cycloalkyl-bearing α-amino acid with an amino functionality and a carboxyl group. The molecule is present as the L-stereoisomer as indicated by its name, and it retains the typical α-amino acid functionality (free amino and free carboxyl) while the cyclobutyl side chain provides a conformationally constrained, hydrophobic character for peptide incorporation studies. L-Cyclobutylglycine is used in peptide synthesis and structure-activity or structure-property investigations to introduce a cyclobutyl side chain that can influence backbone and side-chain conformations, as well as in analytical method development that requires a defined amino acid standard or building block.
CAT No: CP20901
L-Cyclobutylglycine is an L-configured amino acid analog in which the side chain is a cyclobutyl-substituted methylene, giving a conformationally constrained, hydrophobic β/γ-like carbon framework while retaining the canonical amino acid motif with a free or derivatizable carboxyl group and an amino functionality. The stereogenic center at the α-carbon preserves L-stereochemistry, which is critical for stereoselective peptide coupling and for maintaining predictable conformational bias in peptide backbones and peptidomimetic scaffolds. The cyclobutyl side chain provides a compact ring system that can modulate local sterics and backbone/side-chain packing, while the amino and carboxyl groups enable standard protection-group strategies and downstream transformations to esters, amides, and activated coupling partners. As a chiral amino acid building block and synthetic intermediate, L-cyclobutylglycine participates in peptide chemistry workflows and can be converted into functional derivatives for medicinal chemistry and materials-oriented fragment assembly.
1. Peptide Synthesis
L-Cyclobutylglycine is applied in peptide building block preparation where the L-α-amino acid stereocenter supports stereospecific coupling to form amide bonds under standard peptide coupling conditions. The amino group can be protected (for example, as an N-acyl protecting group) to control chemoselectivity during chain elongation, while the carboxyl group can be activated or converted to an ester/acid chloride equivalent depending on the synthetic route. The cyclobutyl side chain functions as a conformationally restrictive hydrophobic substituent that can be incorporated into peptides to probe how steric confinement affects folding propensity and binding-site complementarity. The resulting peptide products and peptide fragments can be used for structure-activity relationship studies and for generating constrained peptidomimetics that retain amino acid compatibility.
2. Peptidomimetics And SAR
L-Cyclobutylglycine is used in peptidomimetic construction and SAR studies because the cyclobutyl side chain introduces a rigid, compact hydrophobe that can bias conformational ensembles relative to flexible alkyl analogs. The amino acid backbone allows conversion into N-protected derivatives and carboxyl-activated intermediates that integrate cleanly into peptide-like scaffolds, including backbone-modified analogs where amide connectivity is preserved. The stereochemistry at the α-carbon enables consistent spatial presentation of the cyclobutyl group, supporting rational comparison of analog series in medicinal chemistry programs. Downstream derivatives prepared from L-cyclobutylglycine can serve as constrained fragments for library synthesis and for mapping structure-property relationships in ligand optimization.
3. Chemical Biology Labeling
L-Cyclobutylglycine is suitable for chemical biology workflows that require incorporation of a chiral amino acid handle into peptides or protein fragments for subsequent functionalization. The amino and carboxyl functionalities enable derivatization into protected intermediates that can be coupled into biomolecule scaffolds, while the cyclobutyl side chain provides a hydrophobic motif that may influence local microenvironment and labeling efficiency. Functional group transformations of the protected amino acid derivative can be used to introduce reactive groups for conjugation strategies, including amide/ester formation and post-coupling modifications that maintain stereochemical integrity. The resulting labeled peptides and conjugation-ready intermediates support biochemical research intermediate preparation for assays that rely on defined stereochemistry and controlled side-chain presentation.
4. Chiral Building Block Synthesis
L-Cyclobutylglycine is employed as a chiral amino acid intermediate in asymmetric or stereocontrolled synthetic routes where preservation of L-configuration is required for downstream stereochemical outcomes. The α-amino acid framework can be selectively protected to manage chemoselectivity between the amine and carboxyl groups during conversion to coupling-ready derivatives such as activated acids or ester intermediates. The cyclobutyl ring withstands common protection-group manipulations and can be carried through multi-step synthesis to generate chiral fragments for peptidomimetic and medicinal chemistry targets. The compound's defined stereochemistry and rigid side-chain geometry make it a practical input for fine chemical synthesis of constrained chiral motifs and for manufacturing-scale intermediate preparation where predictable stereochemical behavior is needed.
5. Process Chemistry Intermediates
L-Cyclobutylglycine is applicable to process chemistry intermediate preparation for pharmaceutical and specialty chemical manufacturing where amino acid derivative handling and controlled protection/deprotection cycles are central to robust synthesis. The amino acid functionality supports conversion into N-protected forms and carboxyl-activated derivatives that can be integrated into peptide coupling steps or further transformed into amide-bearing intermediates. The cyclobutyl side chain provides a stable hydrophobic substituent that can be retained through industrially relevant transformations, enabling consistent impurity profiles and downstream processing compatibility when scaling synthetic routes. The compound can be used to generate reproducible chiral intermediates for constrained scaffold assembly, supporting industrial fine chemical synthesis and applied product development in peptide-based ingredient and intermediate manufacturing contexts.
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