cis-4-Hydroxy-DL-proline is a non-proteinogenic proline derivative featuring a five-membered pyrrolidine ring bearing a hydroxyl substituent at the 4-position and existing as the cis stereoisomer relative to the ring substituents, with a DL designation indicating a racemic mixture at its stereogenic center(s). The molecule contains a free amino group and a free carboxyl group along with a secondary alcohol side-chain, enabling hydrogen-bonding interactions and allowing the hydroxyl functionality to participate in derivatization or to influence conformational preferences during peptide assembly. In peptide chemistry and structure-activity studies, it is used as a stereodefined hydroxyproline analogue for incorporation into synthetic peptides and for preparing more complex amino acid derivatives used in chemical biology, biomaterials research, and analytical method development.
CAT No: CP01106
cis-4-Hydroxy-DL-proline is a hydroxy-substituted proline amino acid featuring a cis relationship between the 4-hydroxyl substituent and the pyrrolidine ring stereochemistry, provided here as a DL (racemic) mixture. The molecule contains a secondary amine within the proline ring and a carboxylic acid, with the hydroxyl group enabling hydrogen-bonding and derivatization chemistry while also influencing conformational preferences typical of proline-based scaffolds. The presence of both an alcohol and an amino functionality makes cis-4-Hydroxy-DL-proline a practical chiral-chemistry intermediate for protected amino acid synthesis, where selective protection strategies can be used to tune reactivity for peptide coupling or downstream functionalization. The racemic stereochemical supply supports method development and library synthesis, while the cis-4-hydroxy substitution can be leveraged to introduce constrained, polar side-chain features into peptidomimetic and protein-interaction studies.
1. Peptide Synthesis
cis-4-Hydroxy-DL-proline is applied in peptide building-block preparation where proline's secondary amine participates in amide bond formation after appropriate N-protection and carboxyl activation. The 4-hydroxyl group can be protected (for example as an ether) to prevent side reactions during coupling, while the cis-4-hydroxy substitution provides a polar, hydrogen-bonding side-chain handle that can affect local conformations in proline-rich sequences. Peptide coupling compatibility is supported by converting the carboxylic acid into an activated ester or protected acid form, enabling stepwise assembly using standard peptide chemistry. The resulting hydroxy-proline-containing peptides can be used as research reagents for conformational analysis, peptide stability studies, and scaffold optimization in synthetic peptide chemistry.
2. Peptidomimetics And SAR Studies
cis-4-Hydroxy-DL-proline is used in peptidomimetic construction and medicinal chemistry research to embed a hydroxyl-bearing proline motif that can modulate binding through hydrogen-bonding and steric constraint. The pyrrolidine ring provides a rigid backbone element, while the cis-oriented 4-hydroxyl group serves as a functional group for further derivatization into ethers, esters, or linkers used in structure-activity relationship studies. Racemic availability supports synthesis of diastereomer-aware libraries and comparative SAR workflows, including approaches that later resolve or selectively incorporate enantiomers. Downstream analog generation from this amino acid intermediate can feed fragment-based molecular design, receptor-binding studies, and conformationally constrained inhibitor or binder optimization.
3. Side-Chain Functionalization
cis-4-Hydroxy-DL-proline is suitable for side-chain functionalization chemistry because the 4-hydroxyl group can undergo controlled transformations without disrupting the proline core. The alcohol can be protected or converted into reactive derivatives such as activated esters or leaving-group-bearing intermediates, enabling attachment of tags, linkers, or solubilizing groups for chemical biology probes. The carboxylic acid and secondary amine allow orthogonal protection strategies, supporting selective modification at one functional site while preserving the other for subsequent coupling steps. Functionalized hydroxy-proline derivatives can be used as intermediates for polymer-bound motifs, affinity reagents, and proline-based linkers in synthetic organic chemistry.
4. Chemical Biology Probes
cis-4-Hydroxy-DL-proline is employed in chemical biology workflows where proline-containing motifs serve as recognition elements in peptide-based probes and protein-interaction assays. The cis-4-hydroxyl substitution introduces a polar side-chain capable of participating in hydrogen-bonding networks, which can be exploited to tune probe binding behavior in a controlled molecular framework. N- and O-protection strategies enable incorporation into labeled peptides or conjugates by ensuring compatibility with coupling chemistry and minimizing hydroxyl interference during synthesis. Probe derivatives prepared from this amino acid can be used to interrogate binding interfaces, evaluate conformational effects, and support assay development for biomolecular recognition studies.
5. Process Chemistry Intermediate
cis-4-Hydroxy-DL-proline is relevant to process chemistry and fine chemical synthesis as a structurally defined amino acid intermediate for manufacturing routes to protected hydroxy-proline derivatives. The combination of a carboxylic acid, secondary amine, and hydroxyl group supports predictable protection-group planning, including N-protection for peptide coupling and O-protection to control chemoselectivity during industrial-scale intermediate preparation. Racemic supply can simplify early-stage synthesis and broaden the range of downstream stereochemical outcomes for later resolution or enantiomer-selective steps when required by the target structure. Industrial intermediate formation from this compound can feed the production of hydroxy-proline building blocks, peptidomimetic precursors, and functionalized amino acid derivatives used across peptide and specialty chemical manufacturing.
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