H-alpha-Me-D-Leu-OH is a D-configured, non-proteinogenic amino acid derivative featuring an α-methyl substitution on the amino acid backbone and a leucine-derived isobutyl side chain, classifying it as an α-substituted amino acid. The molecule contains a free primary α-amino group and a free carboxyl group (-OH), with the α-methyl group increasing steric substitution around the backbone while the side chain remains hydrophobic and aliphatic. As a structurally modified amino acid, it is used in peptide synthesis and structure-activity or conformational studies where α-methylation and D-configuration are employed to probe effects on peptide conformation, stability, and analytical behavior.
CAT No: CP25725
CAS No:29589-63-5
Chemical Name:(R)-a-Methylleucine (>98%, >99%ee)
H-alpha-Me-D-Leu-OH is a chiral amino acid derivative featuring a D-leucine backbone with an alpha-methyl substituent, giving a sterically defined, non-natural residue for stereochemically controlled peptide construction. The molecule contains a free carboxylic acid and a free primary amino group, enabling direct participation in amide bond formation while also supporting salt formation and pH-dependent solubility behavior typical of amino acids. The alpha-methyl stereocenter and the D-configuration at the amino acid carbon framework impose conformational bias that can influence backbone dihedral preferences and side-chain presentation. As a small, single-residue intermediate, H-alpha-Me-D-Leu-OH can function as a chiral building block for protected amino acid synthesis, peptide coupling chemistry, and downstream derivatization where leucine-like hydrophobicity is combined with alpha-substitution.
1. Peptide Synthesis
H-alpha-Me-D-Leu-OH supports peptide building block preparation in peptide synthesis workflows where incorporation of an alpha-methyl, D-configured leucine analog is used to tune steric bulk and backbone conformation. The free carboxylic acid and amino functionality can be converted into coupling-ready derivatives through standard protection strategies, enabling amide bond formation under peptide coupling conditions. The alpha-methyl substituent can affect coupling and subsequent deprotection selectivity when orthogonal protecting groups are employed on the amino and carboxylate. Incorporation of H-alpha-Me-D-Leu-OH-derived residues into short peptides or longer sequences can be used to generate conformationally constrained analogs for structure-function studies and synthetic methodology development in peptide science.
2. Peptidomimetics
H-alpha-Me-D-Leu-OH is suitable for peptidomimetic construction where alpha-methyl substitution and D-configuration are leveraged to modulate proteolytic stability and side-chain display in non-natural peptide scaffolds. The leucine-derived isobutyl side chain provides hydrophobic surface character, while the alpha-methyl center introduces steric and stereochemical constraints that can influence local folding propensity. Derivatization of the amino and carboxyl groups into protected or activated forms enables sequential assembly of peptide analogs and fragment coupling strategies. Downstream use includes generating residue-level variants for molecular design libraries and SAR-oriented optimization of backbone properties using amino acid chemistry principles.
3. Chiral Building Block Development
H-alpha-Me-D-Leu-OH functions as a chiral amino acid intermediate for stereoselective synthesis programs that require a D-leucine-like scaffold with an additional alpha stereocenter. The defined stereochemistry at the alpha position can be carried through as a stable stereochemical element during protection, activation, and coupling steps, supporting consistent stereochemical outcomes in downstream derivatives. Conversion to N-protected forms and carboxyl-activated derivatives enables controlled incorporation into larger molecules, including peptide fragments and non-peptidic chiral targets. The resulting chiral building block utility aligns with fine chemical synthesis, where stereochemical integrity and functional group compatibility are central to manufacturing-relevant route design.
4. Amino Acid Derivatization
H-alpha-Me-D-Leu-OH can be applied to amino acid derivatization strategies that generate functionalized intermediates for chemical biology and synthetic organic chemistry. The presence of both amino and carboxylic acid groups enables formation of amides, esters, and salts, while the alpha-methyl stereocenter provides a handle for tuning steric and electronic effects across derivative series. Protecting-group strategies such as N-protection and temporary carboxyl activation can support selective transformations on side-chain or backbone-adjacent functionalities in multi-step syntheses. Produced derivatives can serve as intermediates for labeled or conjugatable building blocks, enabling downstream scaffold diversification and controlled molecular modifications.
5. Analytical Research
H-alpha-Me-D-Leu-OH is suitable for analytical research and method development where a defined, non-natural amino acid standard supports chromatographic and spectrometric characterization of peptide hydrolysates or synthetic mixtures. The free amino acid functionality supports derivatization workflows used to generate detectable derivatives for LC-MS or GC-based analysis, while the alpha-methyl and D-configuration improve discriminability versus native leucine. Use of H-alpha-Me-D-Leu-OH-derived reference materials can aid in verifying incorporation of alpha-methyl D-leucine residues in synthetic peptides and in monitoring stereochemical integrity during synthesis and deprotection. Analytical deployment in QA/QC-style characterization supports reliable downstream interpretation in peptide chemistry, combinatorial synthesis, and biochemical research intermediate tracking.
6. Pharmaceutical Manufacturing
H-alpha-Me-D-Leu-OH can be employed in pharmaceutical manufacturing contexts as a non-natural amino acid input for producing peptide-based intermediates and controlled stereochemical building blocks used in process chemistry. The amino acid's functional groups enable conversion into protected forms compatible with scalable peptide coupling and purification strategies, including orthogonal protection schemes that facilitate stepwise assembly. The alpha-methyl, D-configured residue can be incorporated to generate peptide fragments with defined conformational features, supporting consistent intermediate quality across manufacturing batches. Downstream utility includes preparation of peptide analogs for process-relevant development work, where robust protection/activation chemistry and stereochemical fidelity are required for reliable intermediate formation in specialty chemical production.
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