6-Methyl-D-tryptophan - ≥97% , CAS No.67008-97-3

CAS: 67008-97-3 Cat. No.: M930072 Formule: C₁₂H₁₄N₂O₂ Poids moléculaire: 218.250

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spécifications et pureté

≥97%

Conditions de stockage de stockage

Room temperature

Pureté

≥97%

Noms et identifiants

Sourires canoniques

CC1=CC2=C(C=C1)C(=CN2)C[C@H](C(=O)O)N

IUPAC Name

(2R)-2-amino-3-(6-methyl-1H-indol-3-yl)propanoic acid

InChIKey

GDMRVYIFGPMUCG-SNVBAGLBSA-N

INCHI

1S/C12H14N2O2/c1-7-2-3-9-8(5-10(13)12(15)16)6-14-11(9)4-7/h2-4,6,10,14H,5,13H2,1H3,(H,15,16)/t10-/m1/s1

Poids moléculaire

218.250

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Indoles and derivatives
      • Subclass Indolyl carboxylic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Indoles and derivatives
• Subclass: Indolyl carboxylic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Indolyl carboxylic acids and derivatives
• Alternative Parents: D-alpha-amino acids 3-alkylindoles Aralkylamines Substituted pyrroles Benzenoids Heteroaromatic compounds Amino acids Monocarboxylic acids and derivatives Carboxylic acids Azacyclic compounds Organic oxides Monoalkylamines Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Indolyl carboxylic acid derivative - Alpha-amino acid - Alpha-amino acid or derivatives - D-alpha-amino acid - 3-alkylindole - Indole - Aralkylamine - Benzenoid - Substituted pyrrole - Heteroaromatic compound - Pyrrole - Amino acid or derivatives - Amino acid - Carboxylic acid derivative - Carboxylic acid - Azacycle - Monocarboxylic acid or derivatives - Primary aliphatic amine - Amine - Hydrocarbon derivative - Organic oxygen compound - Organic nitrogen compound - Carbonyl group - Organic oxide - Organonitrogen compound - Organooxygen compound - Primary amine - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as indolyl carboxylic acids and derivatives. These are compounds containing a carboxylic acid chain (of at least 2 carbon atoms) linked to an indole ring.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Propriétés chimiques et physiques

• Poids moléculaire: 218.250 g/mol
• XLogP3: -0.700
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 218.106 Da
• Monoisotopic Mass: 218.106 Da
• Topological Polar Surface Area: 79.100 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 270.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 1
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

Not applicable. No tested bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic use, refer to the Reaction Conditions and Synthetic Utility tabs for general procedural guidance.

Biological Roles

This compound is an unnatural D-amino acid; it is not one of the 20 proteinogenic L-amino acids. No medical or clinical uses are claimed here; the following are research-focused, literature-based roles.

• Protein engineering and SAR: Used to probe how indole electronics and sterics at position 6 affect protein–ligand interactions when incorporated into peptides or peptide-based scaffolds. Methylation increases hydrophobic surface and can influence π–π and cation–π interactions.
• D-residue effects: Incorporation of D-amino acids into peptides can enhance proteolytic stability and alter secondary structure (e.g., disrupt α-helices or β-strands locally), providing insights into folding and receptor selectivity.
• Enzymology tools: Serves as a stereochemical probe for amino acid transporters, racemases, and peptidases that discriminate between L- and D- forms.
• Photophysics/analytics: Indole chromophore maintains strong absorbance near 280 nm; methylation slightly shifts spectral features, enabling comparative studies of fluorescence quenching and environmental sensitivity (literature observations).
• Metabolic relevance: D-amino acids occur in bacterial cell walls and certain peptides; while 6-methyl substitution is unnatural, it can be used as a model to study transporter promiscuity and metabolic editing.

Note: Actual biological behavior (uptake, metabolism, enzyme recognition) is highly system-dependent; verify compatibility empirically in the relevant organism, enzyme preparation, or cell-free system.

Buffer Applications

This material is an amino acid, but it is not typically used as a primary laboratory buffer. Nevertheless, its acid/base functionality can be leveraged in specialized contexts.

General/literature guidance:

• Acid–base properties: α-COOH pKa ~2.1–2.4; α-NH3+ pKa ~9.1–9.6 (typical amino acid ranges). Consequently, buffering capacity is modest around these pH values but inferior to dedicated buffers (e.g., phosphate, Tris, HEPES).
• Practical use: In peptide coupling or enzymatic assays, minor pH adjustments with dilute NaOH/HCl can solubilize the compound; however, use standard buffers for maintaining reaction pH.
• Recipes: For dissolution, adjust aqueous media to pH 8.5–9.5 to improve solubility (prepare separately buffered media with e.g., borate or carbonate rather than relying on the amino acid itself for buffering).

Recommendation: Employ established buffer systems (phosphate pH 6–8, HEPES pH 6.8–8.2, carbonate pH 9–10.5) for pH control. Use 6-Methyl-D-tryptophan solely as a substrate or building block within those buffered systems.

Green Alternatives

While 6-Methyl-D-tryptophan itself is a solid building block, greener choices pertain to solvents, coupling reagents, and process conditions used with it.

Greener solvent choices (literature/comparison):

• Replace DMF/NMP with: 2-MeTHF, Cyrene, or green polar aprotics (e.g., propylene carbonate) where compatible with coupling chemistry. Water or water–ethanol mixtures for biocatalytic or aqueous-phase couplings.
• Minimize DCM: Use ethyl acetate or 2-MeTHF for extractions and workups when feasible.

Coupling reagent considerations:

• Prefer Oxyma-based systems (e.g., DIC/OxymaPure) over HOBt/HBTU to reduce hazard risk; explore COMU/DEPBT alternatives with lower explosive potential (literature guidance).
• Enzymatic ligation (e.g., sortase, butelase) or aqueous carbodiimide (EDC) methods can reduce solvent and waste, provided the substrate’s solubility allows.

Energy and waste minimization:

• Conduct reactions at ambient temperature when possible; use microwave only if it improves step efficiency.
• Telescoping deprotection–coupling steps reduces solvent exchanges.

Trade-offs:

• Greener solvents may reduce solubility of hydrophobic amino acids; small amounts of co-solvent (ethanol or a limited volume of DMF) may still be necessary.
• Enzymatic methods can demand specific pH/salt conditions and may be slower than uronium couplings.

Summary: Evaluate a matrix of solvent polarity, coupling efficiency, and safety. Start with aqueous/ethanolic or 2-MeTHF systems; escalate to DMF/NMP only if required by solubility and reactivity.

Pharmaceutical Uses

No therapeutic claims are made. Item-specific pharmacopeial status is not provided; consult your regulatory team for use beyond research.

Research/manufacturing context (literature/general):

• Building block: Used in discovery-stage peptide and peptidomimetic synthesis to modulate hydrophobicity and receptor interactions. D-configuration can enhance proteolytic stability in lead optimization.
• Reference standard: Potentially used as an analytical reference for transporter or enzyme assays involving tryptophan analogs.
• Process development: Solubility and crystallization studies for amino acid derivatives; chiral separation method development.

Excipients/formulation: Not typically used as an excipient. If formulated into nonclinical test articles, it is generally present as an active structural component of an investigational research probe rather than a functional excipient.

Compliance notes:

• Grade/purity certification: Not specified for this item; refer to CoA/Spec Sheet.
• Residual solvent and elemental impurity control should follow ICH Q3C/Q3D where applicable in regulated settings; for research use, ensure fitness-for-purpose testing.

Physical Properties

Item-specific specifications are not provided in the Product Data; consult the CoA/Spec Sheet for definitive values.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet. (Amino acids of this type commonly exhibit high melting points with decomposition; literature reports for related tryptophans often >250 °C with dec.)
• Boiling point: Not applicable (decomposes before boiling under ambient pressure; general literature observation for amino acids).
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• pKa (literature, typical amino acids): carboxyl ~2.1–2.4; α-NH3+ ~9.1–9.6; indole N ~16–17 (very weak acid). Exact values depend on substitution and ionic strength.
• Isoelectric point (literature expectation): near pH ~5.5–6 for tryptophan analogs; methyl substitution may shift slightly.
• Solubility (general/literature):
  • Water: moderate at neutral pH (zwitterion); solubility increases in basic aqueous media (deprotonated carboxylate) and decreases in strongly acidic media if the zwitterion aggregates. Hydrotropes or minimal organic cosolvent (e.g., ethanol, DMSO) can aid dissolution.
  • Organic solvents: sparingly soluble in nonpolar media; limited solubility in polar aprotic solvents unless present as salts.
• LogP/logD: Not specified for this item; refer to CoA/Spec Sheet. (Methylation of the indole ring increases hydrophobicity vs. tryptophan.)
• Optical rotation: Not specified for this item; refer to CoA/Spec Sheet. (D-enantiomer will exhibit characteristic [α] dependent on solvent and concentration.)
• UV absorbance (general): strong π–π* band from indole around 280 nm; methyl substitution slightly perturbs λmax and ε (literature).

Quality and Grades

Item-specific grade/purity and stabilizers are not provided in the Product Data. Refer to the CoA/Spec Sheet for assay, residual solvents, water content, and impurity profile.

General guidance on grades relevant to amino acid building blocks:

• Research grade: suitable for routine synthesis, screening, and biochemical experiments where ultra-trace impurities are not critical.
• Peptide synthesis grade (literature/industry usage): emphasizes low inorganic content, low residual solvents, and control of optical purity (ee/er) to minimize racemization and sequence defects.
• HPLC grade (for solvents) is not applicable here; however, “HPLC-verified purity” for solids typically refers to area% by HPLC/UPLC and may be paired with chiral HPLC to confirm enantiomeric excess.
• Optical purity: For D-tryptophan derivatives, enantiomeric ratio (er) and absolute configuration are critical. Verification by chiral HPLC, optical rotation, or derivatization (e.g., Marfey’s) is standard practice (literature best practice).
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. In general, no stabilizer is required for solid amino acids under dry, ambient storage.

What to check on receipt:

• CoA confirms D-configuration and high chemical purity.
• Residual solvents and water (KF) if your application is moisture sensitive.
• Metal content only if relevant to downstream catalysis; otherwise typically not specified.

Reaction and Applications

6-Methyl-D-tryptophan is an unnatural, enantiopure amino acid used as a building block for peptidomimetics, site-specific protein engineering (post-synthetic), and structure–activity studies.

Representative application domains (literature/general):

• Peptide synthesis: Incorporation into peptides to probe indole electronics and sterics; 6-methyl substitution increases hydrophobic bulk and can modulate receptor binding in SAR programs.
• Late-stage diversification: Indole ring provides a handle for electrophilic substitution (e.g., halogenation at 5/7 positions), C–H activation, or N-alkylation (with appropriate protection strategies).
• Bioconjugation: Indole moiety participates in photoinduced electron transfer and can be leveraged in fluorogenic designs; methylation reduces H-bonding at the ring but maintains UV chromophore.
• Enzyme studies: As a D-amino acid analog, it can act as a probe for stereoselective enzymes (racemases, peptidases) and for understanding D-residue tolerance in peptide ligases.

Practical tips:

• Protection strategy: Use Fmoc/Boc on the α-amine and esterification of the carboxyl if required. Indole N is typically protected (e.g., Boc on indole or N-alkyl protection) if harsh conditions are anticipated.
• Solubility management: Dissolve in DMF/NMP or aqueous base prior to coupling; gentle warming and sonication assist dissolution.
• Racemization control: Employ uronium/guanidinium reagents (HATU/HBTU/TBTU) with base such as DIPEA at low temperature and limit exposure time; pre-activate the acid minimally.
• Analysis: Monitor by RP-HPLC at 280 nm; confirm configuration by chiral HPLC or Marfey’s derivatization (literature techniques).

Reaction Conditions

Typical conditions below are literature-based general guidance for amino acid/peptide chemistry; optimize for your specific substrate and scale. No item-specific specifications are implied.

Amide coupling (solution phase):

• Solvent: DMF or NMP (anhydrous). Concentration 0.05–0.2 M.
• Reagents: HATU (1.1–1.5 equiv) or DIC (1.1–1.5 equiv) + Oxyma (1.2–1.5 equiv). Base: DIPEA (2–3 equiv).
• Temperature: 0–25 °C to limit racemization; 1–4 h typical for small fragments.
• Notes: Pre-dissolve amino acid; avoid prolonged pre-activation. Monitor by RP-HPLC (λ = 280 nm).

Solid-phase peptide synthesis (SPPS):

• Resin loading: 0.3–0.7 mmol/g; Fmoc strategy common.
• Coupling: 3–5 equiv of Fmoc-6-methyl-D-Trp derivative with HBTU/HATU + DIPEA, 5–20 min per cycle (microwave can reduce times).
• Deprotection: 20% piperidine/DMF, 2 × 5–10 min; protect indole N if sensitive.

Indole functionalization (electrophilic):

• Halogenation: NBS (1.0–1.2 equiv), DMF, 0–25 °C, minutes to hours; protect α-functions as needed.
• Cross-coupling: Pd(0) catalysts (e.g., Pd2(dba)3/XPhos), base (K3PO4), toluene/DMF, 60–100 °C, 2–12 h after pre-halogenation.

Salt formation/dissolution:

• Dissolve in water adjusted to pH 8.5–9.5 with NaHCO3/Na2CO3; gentle warming and sonication assist dissolution.

Yields: Peptide couplings of hindered tryptophan analogs commonly afford high conversions (>80% crude) under optimized conditions; isolate as needed by preparative HPLC (literature experience).

Safety and Handling

GHS classification and specific hazard statements are not provided in the Product Data. Always consult the SDS for authoritative safety information.

General laboratory safety for amino acid derivatives with indole rings:

• Expected hazards: low acute toxicity relative to many reagents, but may cause irritation to eyes, skin, or respiratory tract. Avoid inhalation of dust and contact with skin/eyes.
• PPE: laboratory coat, safety glasses, and appropriate disposable gloves (e.g., nitrile). Use a dust mask or handle in a fume hood if dusting may occur.
• Incompatibilities: strong oxidizing agents (indole ring can be oxidized); strong acids/bases may cause decomposition over time. Avoid nitrosating conditions.
• Handling tips: minimize exposure to air and light if long-term stability is critical for sensitive applications; indoles can slowly oxidize.
• First aid (overview; defer to SDS):
  • Inhalation: move to fresh air; seek medical advice if symptoms persist.
  • Skin contact: wash with soap and water; remove contaminated clothing.
  • Eye contact: rinse cautiously with water for several minutes; seek medical attention if irritation persists.
  • Ingestion: rinse mouth; seek medical advice.
• Spill response: avoid dust generation; collect mechanically or wet-wipe; dispose of in accordance with local regulations.
• Fire safety: use water spray, CO2, foam, or dry chemical as appropriate for surrounding materials. Combustion may produce CO/CO2 and nitrogen oxides.

Storage guidance: See Storage & Reconstitution tab; follow SDS/label instructions.

Solvent Selection

This product is a solid amino acid building block rather than a bulk solvent. Solvent selection is relevant for dissolution, derivatization, and coupling operations.

• Polarity/miscibility profile (general/literature):
  • Water: moderate solubility at neutral pH (zwitterion); enhanced solubility at basic pH (e.g., pH 9–10). Salt forms (e.g., hydrochloride) can improve aqueous solubility at low pH.
  • Alcohols (MeOH, EtOH): limited to moderate solubility; may aid with co-solvent dissolution.
  • Polar aprotics (DMF, DMSO, NMP): often effective for peptide coupling solutions or for preparing stock solutions when water solubility is insufficient.
  • Nonpolar solvents (EtOAc, hexanes, toluene): poor solubility.

Practical choices by task:

• Peptide coupling (solution phase): DMF, NMP, or DCM/DMF mixtures with base (e.g., DIPEA) are commonly used; add minimal DMSO if needed to fully dissolve the amino component (literature practice).
• Salt formation/extraction: water with pH adjustment enables phase manipulation; use aqueous-organic biphasic systems as needed.
• Analytical HPLC: water–acetonitrile with 0.1% formic acid or TFA for reversed-phase separation of tryptophan analogs; UV detection near 280 nm.

Comparison (literature guidance):

• Water (pH-adjusted) vs. DMF: choose water for biochem workflows; choose DMF/NMP for carbodiimide/uronium couplings where anhydrous conditions and complete dissolution are essential.

Storage and Reconstitution

• Storage conditions (as provided): Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General storage guidance (literature/practice):

• Keep tightly closed in a dry container, protected from prolonged light exposure. Desiccant is recommended to limit moisture uptake.
• Avoid sources of strong oxidants. Normal laboratory ambient storage is acceptable for most amino acid solids.

Reconstitution/dissolution (general suggestions):

• Aqueous: Adjust water to pH 8.5–9.5 with NaHCO3/Na2CO3, then add the solid with stirring; sonicate or gently warm (≤40 °C) if needed.
• Organic: Use DMF, DMSO, or NMP for concentrated stock solutions; dilute into the reaction medium immediately after preparation.
• Filtration: If preparing analytical standards, filter through 0.22 µm PVDF or PTFE to remove particulates.

Solution stability (general):

• Aqueous basic solutions are best prepared fresh. For short-term storage, keep at 2–8 °C protected from light. For longer-term storage of analytical stocks in DMSO or water, aliquot and freeze (−20 °C) to avoid repeated freeze–thaw cycles.

Research use only: As stated in Product Data, this product is for research use only.

Structure and Identity

A D-configured, methyl-substituted tryptophan where the indole ring bears a methyl group at the 6-position; an unnatural amino acid useful as a chiral building block.

• SKU: M930072
• Product name: 6-Methyl-D-tryptophan
• CAS: 67008-97-3
• PubChem CID: 12878500
• InChIKey (as provided): 99174
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet. (Literature for 6-methyl tryptophan suggests C12H14N2O2; see note.)
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (Literature estimate for free amino acid ~218.25 g/mol; see note.)

Structural features (general/literature):

• Core scaffold: indole (bicyclic aromatic system: benzene fused to pyrrole) attached via a methylene to the α-carbon of the amino acid.
• Substitution: methyl group at the 6-position of the indole ring (ring carbon adjacent to the 5-position of the benzene portion), increasing hydrophobicity vs. tryptophan.
• Functional groups: α-amino (–NH2/–NH3+ depending on pH), α-carboxyl (–COOH/–COO–), indole NH (weakly acidic), aromatic methyl (electron-donating).
• Stereochemistry: D-configuration at the α-carbon (S absolute configuration using CIP rules for common D-amino acids derived from D- glyceraldehyde reference).

2D description in words:

• The α-carbon is bonded to: (i) an amino group, (ii) a carboxylate/carboxylic acid, (iii) a methylene that connects to C3 of an indole ring, and (iv) a hydrogen. The indole ring carries a methyl substituent at its 6-position on the benzene ring.

Synthetic Utility

6-Methyl-D-tryptophan is a versatile chiral building block combining an indole heteroaromatic with an α-amino acid handle.

Key reactivity (literature/general):

• Indole chemistry: Electrophilic substitution at positions 5 and 7 remains accessible; methyl at C6 directs and modulates reactivity. N1 alkylation/acylation possible under basic conditions; protect indole N if undesired.
• α-Carboxyl activation: Formation of active esters (e.g., OSu, OPfp) or uronium-mediated activation (HATU/HBTU/COMU) enables amide bond formation to give peptides and peptidomimetics.
• Orthogonal protections: Fmoc/Boc on the α-amine; benzyl or tert-butyl esters on the carboxyl; indole N protection (e.g., Boc, SEM) for stability under electrophilic conditions.
• Cross-coupling after prefunctionalization: Halogenation of the indole ring (e.g., NBS/NIS) followed by Suzuki/Miyaura or Buchwald–Hartwig methodologies to introduce diverse substituents.
• Oxidation/functionalization: Mild oxidation at benzylic positions is limited; C–H activation strategies may be applied with appropriate directing groups.

Retrosynthetic value:

• Provides a pre-installed D-stereocenter at the α-carbon, avoiding asymmetric induction during peptide assembly. The 6-methyl substituent serves as a steric probe in SAR campaigns and can bias conformations in macrocyclizations.

Analytical/QA:

• Confirm structure by 1H/13C NMR (diagnostic methyl singlet on the aromatic ring; indole resonances), HRMS, and chiral HPLC to verify enantiopurity.

Target Specificity

Not applicable. This product is a small-molecule amino acid building block, not an antibody, enzyme, or affinity reagent. No antigen/epitope or species reactivity is relevant.