3-(4-Methoxytritylthio)propionic acid - ≥97% , CAS No.383401-15-8

CAS: 383401-15-8 Cat. No.: M971008 Summenformel: C₂₃H₂₂O₃S Molekulargewicht: 378.5 PubChem CID: 15508382

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥97%

Storage

Room temperature

Reinheit

≥97%

Namen und Kennungen

• Kanonisches Lächeln: COC1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3)SCCC(=O)O
• IUPAC Name: 3-[(4-methoxyphenyl)-diphenylmethyl]sulfanylpropanoic acid
• InChIKey: SZUNYBJVQYEMOW-UHFFFAOYSA-N
• INCHI: 1S/C23H22O3S/c1-26-21-14-12-20(13-15-21)23(27-17-16-22(24)25,18-8-4-2-5-9-18)19-10-6-3-7-11-19/h2-15H,16-17H2,1H3,(H,24,25)
• Isomere SMILES: COC1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3)SCCC(=O)O
• PubChem CID: 15508382
• Molekulargewicht: 378.5

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Klasse Triphenyl compounds

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Triphenyl compounds
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Triphenyl compounds
• Alternative Parents: Phenoxy compounds Methoxybenzenes Anisoles Alkyl aryl ethers Sulfenyl compounds Monocarboxylic acids and derivatives Dialkylthioethers Carboxylic acids Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Triphenyl compound - Phenoxy compound - Anisole - Methoxybenzene - Phenol ether - Alkyl aryl ether - Monocyclic benzene moiety - Carboxylic acid derivative - Carboxylic acid - Ether - Monocarboxylic acid or derivatives - Dialkylthioether - Thioether - Sulfenyl compound - Hydrocarbon derivative - Organooxygen compound - Organosulfur compound - Carbonyl group - Organic oxygen compound - Organic oxide - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as triphenyl compounds. These are aromatic compounds containing a triphenyl moiety.
• 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 378.500 g/mol
• XLogP3: 5.000
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 8
• Exact Mass: 378.129 Da
• Monoisotopic Mass: 378.129 Da
• Topological Polar Surface Area: 71.800 Ų
• Heavy Atom Count: 27
• Formal Charge: 0
• Complexity: 429.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• 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

No vendor-validated biological assay protocols are provided for this small-molecule building block. Representative laboratory workflows (general literature guidance):

• Solution-phase amide coupling (example): Dissolve the acid (1.0 eq) and amine (1.1–1.5 eq) in dry DMF (0.05–0.2 M). Add HATU (1.1 eq) and DIPEA (2.5 eq) at 0 °C; stir to rt for 1–2 h. Quench with water, extract with EtOAc, wash, dry, and purify.
• On-resin installation (SPPS): After Fmoc deprotection, treat resin with a solution of the acid (3–5 eq), DIC (5 eq), and Oxyma (5 eq) in DMF or DCM for 1–2 h. Wash thoroughly.
• Selective Mmt removal: Treat with 1–3% TFA in DCM containing 2% triethylsilane for 2–5 min cycles. Monitor the yellow trityl color; repeat until complete. Neutralize and wash extensively.
• Thiol conjugation (maleimide): Dissolve the deprotected thiol derivative in degassed phosphate buffer (pH 6.8–7.0). Add maleimide partner (1.1 eq) under N2; stir 30–60 min at rt. Purify promptly to avoid disulfide formation.

These are non-validated, illustrative procedures. Optimize stoichiometry, solvent, and time for your specific substrates and scales. Always perform small-scale trials first.

Biological Roles

This product is a synthetic, protected small-molecule linker rather than a native metabolite. It functions as a chemical tool to introduce a thiol group after selective deprotection.

• Role in bioconjugation workflows (general): The Mmt group allows temporary masking of a thiol during assembly of peptides, oligonucleotide conjugates, or protein adducts. Following coupling of the acid to a biomolecule amine, mild acidolysis yields a free thiol, which can then participate in selective reactions (e.g., Michael addition to maleimides, thiol–disulfide exchange) under near-physiological conditions.
• Orthogonality: Because Mmt is cleaved with very dilute acid, it can be orthogonal to Fmoc (base-labile) and to tBu/Boc protections (strong acid-labile), enabling staged functionalization in complex biomolecule syntheses (literature).
• Spacer effects: The 3‑carbon (propionic) linker provides flexibility and distance, aiding accessibility of the liberated thiol to coupling partners and surfaces (e.g., Au–S interactions for surface assembly after deprotection).

No medical or clinical activity is implied. Use is restricted to laboratory research. For biological assays or conjugations, ensure removal of residual trityl-derived byproducts after deprotection (scavenger washes, thorough resin/solution rinses) to avoid nonspecific interactions in downstream biological systems.

Buffer Applications

This compound is not a buffering agent and does not define a specific pH buffering system. It is a protected thiol-bearing carboxylic acid building block.

Practical notes (general):

• If aqueous coupling is required (e.g., bioconjugation to proteins), convert to the NHS ester in anhydrous organic solvent, then introduce into buffered aqueous media (pH 7.2–8.0, phosphate or bicarbonate), keeping exposure brief to minimize hydrolysis. Alternatively, perform carbodiimide (EDC) coupling in MES buffer (pH ~4.5–6) with NHS or sulfo‑NHS accelerants (literature guidance).
• Mmt deprotection is typically done in organic media with dilute TFA. It is not performed in standard biological buffers.

Green Alternatives

Greener choices relate primarily to solvent and reagent selection around coupling and Mmt deprotection; the core protecting group strategy offers mild, selective thiol unveiling that can avoid heavy‑metal deprotections used by other groups (e.g., Acm → Hg2+/I2).

Options and tradeoffs (literature):

• Replace DCM in deprotection with 2‑MeTHF or EtOAc:
  • Pros: lower toxicity/halogen-free; better EHS profile.
  • Cons: Mmt solubility and acidolysis rates may be reduced; method re-optimization required.
• Use lower‑GWP acids/scavengers:
  • Very dilute TFA in greener solvents; consider formic acid or HCO2H/TES combinations where compatible. Note that Mmt removal efficiency is highest with TFA; alternatives may be slower.
• Coupling reagents:
  • Swap HATU/HBTU (uronium salts with HFIP byproducts) for EDC·HCl/Oxyma or DIC/Oxyma in EtOAc/2‑MeTHF when moisture-tolerant conditions are acceptable.
• Minimize DMF/NMP exposure:
  • Prefer MeCN or 2‑MeTHF when substrates allow; or run at higher concentration to cut solvent volume.

Quick comparison (general):

• Conventional: DCM + 1–3% TFA, HATU/DIPEA in DMF.
• Greener variant: EtOAc or 2‑MeTHF + dilute TFA (validated experimentally), EDC·HCl/Oxyma in EtOAc with catalytic DMAP.

Note: Validate deprotection kinetics and product integrity when departing from standard DCM/TFA protocols.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided for this item. It is supplied for research use only.

Contextual, non-clinical information (general):

• As a linker precursor, 3-(4-methoxytritylthio)propionic acid can be used in R&D to install a masked thiol onto small molecules, peptides, or polymers. After deprotection, the thiol can engage in conjugation steps relevant to investigational modalities (e.g., prototype antibody–drug conjugate linkers, PEGylation points, or surface attachments). These are process-development roles, not approved pharmaceutical uses.
• The Mmt group’s high acid lability enables orthogonal protecting-group strategies during multi-step assembly, potentially reducing protecting-group interchange and harsh global deprotection steps.

If regulatory or GMP use is contemplated, obtain full quality documentation (CoA, residual solvents, elemental impurities, stability) and perform internal qualification. Absent item-specific grade information, this listing should be treated strictly as research-grade material.

Physical Properties

Item-specific physico-chemical specifications are not available in the provided product data.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point (literature/analogy): Not broadly reported; many Mmt-protected thiol acids are solids that melt above ambient temperature. Consult the CoA for this lot.
• Boiling point: Not applicable (decomposes before boiling; literature expectation for such polyaryl thioethers).
• Density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• LogP (qualitative, literature/analogy): Expected high lipophilicity due to the triaryl Mmt core; poor aqueous solubility.
• Solubility (literature/analogy): typically soluble in chlorinated and polar aprotic organic solvents (e.g., DCM, DCE, THF, DMF, DMSO, acetonitrile); sparingly soluble to insoluble in water. Actual solubility can vary by lot and form; verify empirically.
• pKa: Carboxyl pKa for analogous 3‑mercaptopropionic acid derivatives ~4–5 (literature). The thioether sulfur is not basic under neutral conditions.

Notes:

• Properties above labeled “literature/analogy” are general expectations based on closely related Mmt‑protected thiol acids and should be verified experimentally for your application.
• For chromatographic method development, begin with DCM/MeOH or DCM/EtOAc gradients; UV absorbance is strong in the 220–280 nm region due to the triaryl chromophore (literature).

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

Context for this class of product (general information for professional users):

• Research grade building blocks are commonly supplied at ≥95% purity by HPLC or NMR assay. When purity matters for downstream bioconjugation or SPPS, verify by vendor CoA and consider in-house qNMR/HPLC.
• Low water content is beneficial for efficient amide coupling (minimizes carbodiimide urea formation and O→N acyl transfer). If Karl Fischer or residual solvent specs are critical for your process, request the batch CoA.
• Stabilizers: This item typically does not require stabilizers; however, prolonged contact with strong acids can cause Mmt cleavage. Avoid storing with acidified desiccants.
• Analytical identity: For triaryl Mmt derivatives, identity is strongly supported by 1H NMR signals near 6.8–7.4 ppm (aryl), benzhydrylic CH around 5–6 ppm (often broadened), OMe near 3.7–3.8 ppm, and aliphatic –CH2–CH2– of the propionate at ~2.5–3.0 and ~2.3–2.6 ppm (literature). MS typically shows the [M–H]− or [M+H]+ corresponding to the protected acid.

Recommendation: Confirm suitability via CoA plus an incoming verification (1H NMR, LC–MS) before scale-up or GMP-adjacent use.

Reaction and Applications

Primary uses derive from its role as an Mmt-protected 3‑mercaptopropionic acid building block.

• Introduction of a masked thiol spacer: Couple the carboxylic acid to amines (solution-phase or on-resin) to install a –CH2–CH2–S–Mmt handle. Subsequent selective Mmt cleavage liberates a free thiol for downstream conjugation (maleimides, haloacetyls, thiol–ene).
• Solid-phase peptide synthesis (SPPS):
  • On-resin N‑terminus or lysine side-chain acylation with this acid introduces a thiol handle orthogonal to Fmoc/tBu protections. Mmt deprotects under very mild acid (e.g., 1–3% TFA in DCM) without removing tBu-based side-chain protections (literature), enabling on‑resin cyclizations or conjugations.
• Bioconjugation/linker chemistry: After amide coupling to proteins/peptides (via NHS ester formation or carbodiimide activation under aqueous-compatible conditions), selective Mmt removal yields a thiol for site-selective coupling to maleimide dyes, PEGs, or surfaces.
• Surface immobilization: The spacer length (–CH2–CH2–S–) provides flexibility and distance from surfaces for gold–thiol self-assembly after deprotection.
• Protecting-group strategy: Mmt is more acid-labile than Trt, enabling staged deprotection sequences; it is removable with dilute TFA, minimizing side reactions compared to global deprotection conditions.

Practical tips (literature):

• Monitor deprotection by the appearance of the characteristic yellow/orange trityl cation in the washings and by test cleavage LC–MS.
• Use nucleophilic scavengers (e.g., triethylsilane, thioanisole) during acidolysis to trap carbocations and suppress arylation.
• Keep coupling media anhydrous to limit thioester formation or O→S acyl transfer side reactions.

Reaction Conditions

General literature guidance for this class of compounds (verify experimentally):

• Amide coupling to amines:

  • Solvent: dry DMF, NMP, or DCM.
  • Reagents: HATU (1.05–1.2 eq) or EDC·HCl (1.2–1.5 eq) with Oxyma or NHS; base DIPEA (2–3 eq).
  • Conditions: 0 °C to rt; 0.5–4 h (monitor by TLC/LC–MS). Typical isolated yields for unhindered partners: 70–95%.
  • Notes: For aqueous-compatible bioconjugation, preform the NHS ester in organic solvent, then react in PBS or bicarbonate buffer (pH 7.4–8.3) for 0.5–2 h at rt.

• Mmt deprotection (selective thiol unveiling):

  • Solvent: DCM (or DCM/MeOH), optionally 2‑MeTHF/EtOAc with validation.
  • Acid: TFA 1–3% v/v; additives: triethylsilane (1–5% v/v), anisole (1–5% v/v) as scavengers.
  • Time: 2–15 min cycles; repeat until yellow/orange trityl color diminishes and test cleavage shows completion.
  • Temperature: rt.
  • Workup: Neutralize with base (e.g., pyridine) or wash with saturated NaHCO3 carefully; remove scavengers and trityl byproducts by thorough washing/extraction.

• Post-deprotection thiol conjugation:

  • Maleimide coupling: pH 6.5–7.0, phosphate buffer, 30–120 min at rt; minimize oxygen to limit disulfide formation.
  • Haloacetyl coupling: pH 7.5–8.5, 0–25 °C, 0.5–2 h.

These conditions are representative of literature practices and may need adjustment for your substrates and scale.

Safety and Handling

GHS classification, signal word, and hazard statements are not provided in the product data and may vary by jurisdiction and supplier lot. Always consult the product SDS for authoritative safety information.

• GHS/CLP: Not specified for this item; refer to SDS.
• Likely hazards (general chemistry knowledge): carboxylic acids may cause skin/eye irritation; aryl thioethers and their vapors/dusts can be irritating and may have a strong odor. Mmt deprotection liberates a strongly colored trityl cation in acidic media; handle acid mixtures with care.
• Incompatibilities: strong oxidizers (risk of sulfoxide/sulfone formation), strong bases (possible hydrolysis in protic media), strong acids may trigger premature Mmt cleavage. Avoid nitrosating agents.
• PPE: lab coat, nitrile gloves, safety glasses; use in a fume hood. For acidolysis/deprotection work, consider acid-resistant gloves and face protection.
• Handling tips: keep containers tightly closed; minimize exposure to acids to prevent unintended deprotection. For weighing, avoid static and dust generation.
• First aid (overview; defer to SDS): rinse skin/eyes with water upon contact; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth and seek medical attention. Show SDS to physician.
• Spill response: absorb with inert material (vermiculite, sand), collect for disposal. Wash contaminated surfaces with appropriate solvent and then detergent solution.
• Waste: treat as organic laboratory chemical waste; acidolysis residues containing TFA/scavengers must be collected separately per institutional and regulatory guidelines.

Solvent Selection

This compound is a lipophilic, acid-bearing aryl thioether. Solvent choice is driven by task: dissolution for amide coupling, chromatographic handling, or deprotection.

• Polarity/miscibility (literature/analogy):
  • High solubility: DCM, DCE, chloroform, THF, DMF, NMP, DMSO, MeCN.
  • Moderate: EtOAc, toluene (warm).
  • Poor/insoluble: water, alkanes.
• For amide coupling: use dry DMF, NMP, or DCM with base (DIPEA) and coupling agent (HATU/HBTU/EDC). DMF/NMP maximize solubility with polar amines; DCM favors rapid activation with carbodiimides when substrates are lipophilic.
• For workup: EtOAc/hexane or DCM/MeOH systems are effective; the Mmt chromophore enables UV monitoring at 254 nm.
• For purification: normal-phase silica with DCM→DCM/MeOH or DCM/EtOAc gradients. For sensitive targets, reverse-phase C18 (ACN/H2O + 0.1% acid) after esterification of the acid function to prevent tailing.
• Deprotection media: dilute TFA in DCM (e.g., 1–5% v/v) with scavengers (triethylsilane, anisole) is customary for Mmt removal (literature). Use glassware resistant to acid and maintain good ventilation.

Comparison (literature/analogy):

• DCM vs DMF: DCM offers easy removal and lower polarity (good for acidolysis); DMF maximizes solubility for polar coupling partners but is harder to remove and less green.

Storage and Reconstitution

• Storage Conditions (product data): Room temperature.
• General storage guidance: Keep tightly closed in a dry, inert atmosphere (desiccator with non-acidic desiccant). Protect from strong acids to prevent premature Mmt deprotection. Store away from oxidizers and light sources that may promote degradation of aryl thioethers.
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution/Preparation:
  • For solution use, dissolve in anhydrous organic solvents (e.g., DCM, DMF, DMSO, MeCN). Filter if particulates are present. Use freshly prepared solutions for coupling or deprotection steps; prolonged storage in solution may lead to hydrolysis or oxidation.
  • For SPPS, prepare standard coupling cocktails (e.g., DIC/Oxyma or HATU/DIPEA) immediately before use.
• Freeze–thaw: Not typically applicable to dry solids. If storing stock solutions, aliquot and store under inert gas at low temperature (e.g., 2–8 °C) to limit oxidation; allow to warm to room temperature before opening to avoid moisture ingress.
• Stability notes (general): Mmt-protected thioethers are stable under neutral/basic, non-oxidizing conditions. Avoid exposure to strong acids and oxidants. Confirm integrity by NMR/LC–MS prior to critical applications.
• Research Use Only: For research use only (product data).

Structure and Identity

3-(4-Methoxytritylthio)propionic acid is a thiol-masked carboxylic acid building block in which the sulfur of 3-mercaptopropionic acid is protected as a 4-methoxytrityl (Mmt) thioether. The molecule comprises a benzhydrylic (trityl-like) center bearing two unsubstituted phenyl rings and one para‑methoxyphenyl ring, attached through the benzylic carbon to sulfur; the sulfur is then tethered by a –CH2–CH2– to a terminal carboxylic acid. Key features include: a para‑methoxy-substituted triphenylmethyl core (electron-rich aryl system), a thioether linkage (S–C), and a terminal carboxyl group.

• SKU: M971008 (Aladdin Scientific)
• CAS: 383401-15-8 (product data)
• PubChem CID: 15508382 (product data)
• InChIKey: 349707 (as provided; note: non-standard length as supplied in product data)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.

Structural description (2D, in words): an Mmt group [(4‑methoxyphenyl)diphenylmethyl] bound to sulfur (Mmt–S–), followed by a two‑carbon aliphatic chain ending in –CO2H (…–S–CH2–CH2–CO2H). No stereocenters are present in the backbone; the benzhydrylic center is trigonal (sp2-like cation-stabilized framework when ionized during deprotection). Functional groups: aryl ether (–OCH3), thioether (–S–), and carboxylic acid (–CO2H).

Synthetic Utility

Functional elements and reactivity:

• Carboxylic acid: amenable to standard coupling (carbodiimide, uronium, phosphonium reagents) to form amides/esters. Can be transformed to activated esters (NHS, Pfp) or acyl chlorides under anhydrous conditions.
• Thioether bearing Mmt: the sulfur is masked; Mmt is removable under mild acid to reveal a free thiol (–SH). The liberated thiol participates in Michael additions (maleimides, acrylates), thioetherifications (haloacetyls), thiol–ene reactions, or disulfide formation/reshuffling.

Named/standard operations (literature):

• Coupling: HATU/DIPEA in DMF; EDC·HCl/NHS or DIC/Oxyma in DCM/DMF; PyBOP/DIPEA for hindered amines.
• Selective deprotection: 1–3% TFA in DCM with triethylsilane or anisole scavengers; multiple short treatments until deprotection is complete (monitor by color and test cleavages).
• On-resin manipulations (SPPS): Acylate N‑terminus or Lys side chain, deprotect Mmt selectively, then perform on‑resin cyclization (e.g., thiol–maleimide) or capture with electrophiles.

Retrosynthetic value:

• Serves as a convenient masked equivalent of 3‑mercaptopropionic acid that tolerates bases and many nucleophiles during upstream steps, deferring thiol chemistry to a late stage.

Caveats:

• Avoid strong oxidants to prevent S→O oxidation (sulfoxide/sulfone). Keep acidolysis brief and employ scavengers to minimize arylation or overalkylation by trityl cations.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological targeting reagent (e.g., antibody, ligand, or inhibitor). No antigen, epitope, species reactivity, clone, or isotype information applies.