N-α-Methyl-D-alanine is a non-proteinogenic, D-configured amino acid derivative in which the α-amino acid backbone bears an N-methyl substituent at the α-amino nitrogen, distinguishing it from unmodified alanine. The molecule contains a free carboxyl group and a methylated amino functionality, with the stereochemistry specified as D at the α-carbon and the side chain corresponding to a methyl group typical of alanine analogues. In peptide and peptidomimetic synthesis, N-α-methylation alters backbone hydrogen-bonding and conformational behavior, making this compound a substrate or building block for structure-activity studies, chemical biology labeling strategies, and the preparation of modified amino acid residues in synthetic peptides.
CAT No: CP00135
N-α-Methyl-D-alanine is a chiral, D-configured amino acid derivative featuring an α-methyl substituent that increases steric bulk around the stereogenic center and modulates conformational preferences relative to alanine. The molecule contains a free primary amino group and a carboxylic acid, enabling standard amino acid coupling chemistry while also supporting selective derivatization of the amino and acid functionalities. The D stereochemistry provides a predictable chiral handle for stereoselective synthesis, peptide incorporation, and downstream analytical discrimination. The α-methyl substitution can influence amide bond geometry, backbone rigidity, and resistance to proteolytic cleavage in peptide contexts, making it a practical intermediate for amino acid derivatization and peptide science workflows.
1. Peptide Synthesis
N-α-Methyl-D-alanine is used in peptide synthesis and peptidomimetic assembly where D-amino acid incorporation and α-methyl-induced steric effects are leveraged to tune backbone conformation and local sterics. The free amino and carboxylic acid groups allow conversion to protected forms for peptide coupling, such as N-protected derivatives and activated carboxylic acid equivalents compatible with standard amide bond formation. The presence of the α-methyl stereocenter supports stereochemically defined incorporation into growing peptide chains, enabling systematic studies of how D-configuration and α-substitution alter coupling outcomes and resulting peptide conformations. Downstream, N-α-methylated D-alanine residues can be introduced into short peptides, cyclic scaffolds, and protease-challenging analogs for structure-function investigations and synthetic methodology development.
2. Chiral Building Blocks
N-α-Methyl-D-alanine functions as a chiral amino acid intermediate for stereoselective synthesis of enantiopure compounds and for constructing chiral centers adjacent to amide or ester linkages. The D configuration and α-methyl substituent provide a defined stereochemical motif that can be transferred into higher-complexity fragments through derivatization of the amino and carboxyl groups. Selective protection strategies, such as temporary N-protection and controlled carboxyl activation, can be employed to manage chemoselectivity during sequential functional group transformations. The resulting chiral building blocks are suitable for fine chemical synthesis where stereodefined aliphatic amino acid motifs are required for downstream fragment coupling, SAR-focused analog generation, and chiral analytical reference preparation.
3. Amino Acid Derivatization
N-α-Methyl-D-alanine is applied in amino acid derivatization workflows to generate functionalized amide, ester, and activated carboxyl derivatives used as intermediates in synthetic organic chemistry. The amino group can be protected or functionalized to introduce handles for further coupling, while the carboxylic acid can be converted into acylating agents, mixed anhydrides, or ester intermediates to support controlled downstream transformations. The α-methyl substitution can influence reactivity patterns and steric accessibility, which may be exploited when designing stepwise syntheses that require predictable chemoselectivity around the α-position. Generated derivatives can serve as intermediates for building peptidomimetic linkers, preparing chiral ligands, or producing labeled and derivatized standards for analytical method development.
4. Chemical Biology Probes
N-α-Methyl-D-alanine is suitable for chemical biology research where D-amino acid content and α-methyl substitution are used to modulate peptide backbone behavior in binding and recognition studies. The amino acid functionality enables incorporation into peptide probes, affinity tags, or scaffold fragments that can be coupled to biomolecular targets through standard amide-forming chemistries after appropriate protection and activation. The D stereochemistry provides a chiral signature that can be used to distinguish probe stereochemistry in structure-activity relationship studies and to evaluate how backbone stereochemistry affects molecular recognition. Downstream, α-methylated D-alanine-containing constructs can be used to prepare analog libraries for biochemical assays, enabling systematic exploration of sequence-dependent effects in peptide science.
5. Pharmaceutical Manufacturing Intermediates
N-α-Methyl-D-alanine is used in pharmaceutical intermediate preparation for producing stereochemically defined amino acid building blocks that can feed into peptide-like active ingredient fragments and process-compatible synthesis routes. The presence of both amino and carboxylic acid groups supports conversion into protected amino acid forms and activated intermediates that align with common manufacturing strategies for controlled amide bond formation. The α-methyl substitution can be incorporated into drug-like scaffolds to tune physicochemical properties and stability of peptide-derived structures during downstream synthesis and formulation development. Generated protected or activated derivatives can be manufactured at scale as well-defined intermediates for fine chemical production, supporting consistent stereochemical outcomes across batch-to-batch peptide assembly steps.
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