This compound belongs to the class of organic compounds known as carboxylic acid esters. These are carboxylic acid derivatives in which the carbon atom from the carbonyl group is attached to an alkyl or an aryl moiety through an oxygen atom (forming an ester group).
External Descriptors
Not available
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.
Determine the necessary mass, volume, or concentration for preparing a solution.
Dilution Calculator
Determine the dilution needed to prepare a stock solution.
Reconstitution Calculator
Revisões
Avaliações dos Clientes
Application Protocols
No vendor-validated assay protocols are provided for this item. Below are general, literature-style procedures for research use only.
SPPS coupling (general):
Swell resin in DCM (optional), then exchange to DMF.
Prepare a solution of Fmoc-AA (4–5 equiv), TOTU (4–5 equiv) in DMF; add DIPEA (8–10 equiv). Mix briefly and transfer to resin.
Agitate 15–30 min at RT. Wash resin thoroughly with DMF, then proceed to capping or next cycle.
Solution-phase amidation (general):
To a stirred solution of carboxylic acid (1.0 equiv) and DIPEA (2.0–3.0 equiv) in anhydrous DMF/DCM, add TOTU (1.0–1.2 equiv) at RT.
After 0–5 min, add the amine (1.0 equiv) and stir until completion (TLC/LC–MS). Quench, extract, and purify.
Notes:
Use anhydrous solvents and inert atmosphere to maximize efficiency.
For sequences prone to epimerization, minimize pre-activation time and operate at lower temperatures.
For instrument-specific, validated protocols (e.g., automated synthesizers), consult platform documentation and perform method development with small-scale scouting couplings.
Biological Roles
TOTU is a synthetic coupling reagent and has no intrinsic biological role, metabolism, or signaling function. Its relevance to life sciences arises from its utility in assembling peptides and amide-containing molecules used in research. Any interaction with biological systems is incidental to residual reagent/byproducts and should be avoided.
Not a nutrient, metabolite, enzyme substrate, or inhibitor by design.
Not used in cell culture as a component; residuals should be removed by purification before any biological testing of synthesized products.
Handle strictly as a laboratory chemical; do not introduce into biological systems except as trace contaminants to be minimized during synthesis and workup.
For any work intended to interface with biological assays, ensure thorough purification (e.g., preparative HPLC for peptides) and analytical confirmation that coupling reagent residues and triazole byproducts are below method detection limits.
Buffer Applications
Not typically applicable. TOTU is not a buffering agent and is incompatible with aqueous/protic buffer systems due to rapid hydrolysis and deactivation.
Practical note: Perform coupling reactions in anhydrous organic solvents. If aqueous workup is required after coupling, quench and extract promptly; do not attempt to formulate aqueous buffers containing TOTU.
Green Alternatives
Greener process considerations focus on solvent and additive choices around TOTU, as the core reagent function is often difficult to replace without performance tradeoffs.
Options and tradeoffs (literature):
Solvent substitution:
Replace DCM with EtOAc, CPME, or 2-MeTHF for resin swelling or solution-phase amidations; may require longer times or temperature elevation for equivalent conversions.
Substitute DMF with NBP, NMP alternatives (where permitted), or propylene carbonate; monitor viscosity and diffusion in SPPS cycles.
Alternative coupling systems:
COMU (Oxyma-based uronium) with greener solvents can reduce hazardous byproducts and sometimes improve coupling efficiency, but cost and supply considerations apply.
Carbodiimide (EDC) + Oxyma/HOAt/HOBt surrogates in aqueous-organic media can be greener for small molecules; however, SPPS performance and epimerization control may be inferior for difficult sequences.
Comparison snapshot (general):
TOTU vs HBTU/TBTU: avoids benzotriazole leaving group; similar operational profile.
TOTU vs COMU: COMU often shows enhanced coupling and lower epimerization with Oxyma chemistry; TOTU may be simpler to handle/regulatory-friendly depending on jurisdiction.
Process intensification: Lower solvent volumes, higher-concentration couplings, and microwave/heat-assisted protocols (while controlling side reactions) can reduce energy and waste.
Recommendation: Begin with DMF or NBP at the lowest effective volume; consider DCM-free resin swelling (e.g., pure DMF/NMP) where resin and sequence permit. Validate at small scale before adopting at production scale.
Process reagent: TOTU can be used as a process coupling reagent in the synthesis of peptide drug substances and amide-bearing intermediates. It is consumed during reaction and removed during downstream purification.
Regulatory considerations: Selection among coupling reagents (e.g., TOTU vs HBTU/TBTU/HATU/COMU) may be influenced by impurity profiles, residual risks, and supply chain factors. Document clearance strategies for residual triazole/uronium byproducts per ICH Q3A/Q3C (as applicable).
Equipment compatibility: Reagent is compatible with common SPPS synthesizers and manual peptide assembly setups using DMF/NMP/DCM. Validate elastomer compatibility for seals when using acetonitrile or mixed solvent systems.
Quality control: Implement in-process controls for coupling completeness (e.g., ninhydrin/Kaiser, chloranil tests in SPPS) and final impurity profiling by LC–MS/UPLC.
Environmental, health, and safety (EHS): Engineering controls and PPE to limit operator exposure to dust; solvent management plans for DMF/DCM replacement or reduction can aid in greener filings.
Note: Any use in pharmaceutical manufacturing must ensure removal of reagent and byproducts to acceptable levels; the final drug product must be free from TOTU.
Physical Properties
Item-specific specifications (this product):
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
General/literature characteristics (for guidance only; verify against the CoA/SDS for your lot):
Physical state: typically a moisture-sensitive solid (literature).
Solubility: high solubility in polar aprotic organic solvents commonly used for couplings, such as DMF, NMP, DMAc, DCM, and acetonitrile (literature). Limited solubility in nonpolar hydrocarbons (literature).
Hygroscopicity: can absorb moisture; activity may decline upon prolonged air exposure (literature).
Stability: decomposes in protic media and in the presence of bases over extended time; sensitive to water and light (literature), aligning with the recommended protected-from-light, low-temperature storage.
Typical sensory traits: off-white to beige solid are commonly reported for uronium reagents (literature), but appearance for this item is not specified.
Common computed/literature parameters (ranges; not item specifications):
Melting/decomposition: many uronium salts show decomposition before a sharp melt; values vary by counterion and leaving group.
Partition behavior: designed for use in polar organic media; not intended for octanol/water partition assessment.
Always consult the product’s CoA and SDS for definitive properties when designing processes or QC methods.
Quality and Grades
Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
Context and guidance:
Peptide synthesis grade: When designated, implies stringent control of water content, low halide/metal impurities, and performance in SPPS (low racemization, high coupling efficiency). Absent an explicit grade here, consult the CoA for assay, residual solvents, water (KF), and ancillary tests.
UV/Chromatography considerations: Uronium reagents can absorb in the UV; if using in HPLC-monitored processes, ensure solvent and reagent quality meet your analytical needs (HPLC-grade solvents recommended for solution prep).
Stabilizers: Some coupling reagents are supplied with stabilizers or as specific counterion salts (e.g., BF4− vs PF6−) to balance reactivity/stability. No stabilizer information is provided for this item; refer to the CoA/SDS.
Lot-to-lot verification: Confirm key QC metrics relevant to your use-case (assay by 1H NMR/elemental analysis, water by KF, identity by MS/IR, performance test in a short SPPS coupling) before scale-up.
Performance notes: If using in automated peptide synthesizers, verify particulate level/solubility in your solvent system to prevent valve or frit fouling.
Contact Aladdin Scientific for documentation (CoA, TDS) linked to the specific lot you intend to use.
Reaction and Applications
Primary application: Efficient amide bond formation in peptide synthesis (SPPS and solution-phase), activating carboxylic acids in situ as O-acyluronium intermediates.
Use cases (literature/practice):
SPPS couplings of Fmoc-protected amino acids to resin-bound amines using TOTU + tertiary base (e.g., DIPEA, NMM). Suitable for standard and many hindered residues.
Solution-phase amidations for small-molecule synthesis when benzotriazole-based reagents are to be avoided; triazolyl leaving group can offer favorable reactivity and reduced byproduct coloration.
Minimizing racemization: The fast acylation kinetics of uronium/triazolyl systems can limit oxazolone formation relative to carbodiimide-only methods; consider additives (e.g., Oxyma) case-by-case if further suppression is needed.
Couplings of sterically hindered or electron-poor acids: Often improved versus carbodiimides; adjust base equivalents and reaction time.
Practical notes:
Typical equivalents: 1.0–1.2 equiv acid, 1.0–1.2 equiv TOTU, 2.0–3.0 equiv base to 1.0 equiv amine (literature guidance).
Order of addition: Dissolve acid and base in anhydrous DMF/NMP, add TOTU to pre-activate briefly (0–5 min), then add to the amine/resin; or combine all at once for on-resin couplings to minimize side activation.
Side products: Urea byproducts and triazole derivatives; proper washing and cleavage protocols remove them in SPPS.
Comparators: HBTU/TBTU/HATU/COMU—TOTU offers a non-benzotriazole leaving group profile with performance akin to other uronium reagents; selection can be based on sequence behavior and regulatory preferences.
All applications are for research/laboratory use only.
Reaction Conditions
General literature guidance (verify and optimize for your substrates):
Typical SPPS coupling (Fmoc strategy):
Solvent: DMF or NMP (anhydrous). Optional DCM pre-swell for PS resins.
Equivalents: 3–5 equiv Fmoc-AA (relative to resin loading), 3–5 equiv TOTU, 6–10 equiv base (DIPEA or NMM).
Temperature/time: RT, 5–30 min for standard residues; extend to 45–90 min or recouple for hindered sequences.
Monitoring: Kaiser or chloranil test for completion; double coupling as needed.
Solution-phase amidation:
Solvent: DMF, DCM, ACN, or mixtures (anhydrous).
Equivalents: 1.0–1.2 equiv acid, 1.0–1.2 equiv TOTU, 2.0–3.0 equiv tertiary base per 1.0 equiv amine.
Order: Pre-activate acid with base and TOTU for 0–5 min at RT, then add amine; or add all together to minimize side activation.
Temperature: RT to 40 °C as needed for sluggish couplings; avoid prolonged heating to limit side reactions.
Bases: DIPEA, NMM, collidine; choose weaker bases for acid-sensitive substrates.
Additives: For difficult couplings, consider additives (e.g., Oxyma or HOAt analogs) if compatible with your regulatory constraints; always validate epimerization.
Workup: Quench with dilute amine or bicarbonate, extract with suitable solvent, and purify by chromatography or crystallization. For SPPS, follow with standard wash/deprotection cycles.
Yields: Highly substrate-dependent; quantitative conversions are common on resin for standard residues, while sterically hindered or β-branched cases may require recoupling.
Safety and Handling
Item-specific hazard data:
GHS classification: Not specified for this item; refer to SDS.
Signal word / H-statements / pictograms: Not specified for this item; refer to SDS.
General safety guidance for uronium peptide coupling reagents (literature/practice):
Hazards: May cause skin/eye irritation and respiratory irritation. Avoid dust formation. Some uronium salts can release corrosive/irritant species upon hydrolysis.
Peroxide formation: Not applicable (non-ether); however, hydrolysis can generate acidic/byproduct species—handle in a well-ventilated fume hood.
PPE: Lab coat, safety glasses or splash goggles, and appropriate chemically resistant gloves (e.g., nitrile). Use in a certified fume hood to avoid inhalation of dust/aerosols.
Handling: Minimize exposure to air and moisture. Open containers under inert atmosphere when possible; promptly recap. Prepare solutions with anhydrous solvents.
Incompatibilities: Water, strong bases or nucleophiles (premature decomposition), strong oxidizers, and strong acids (can accelerate degradation). Avoid prolonged contact with alcohols/protic solvents.
First aid overview (consult SDS for details):
Inhalation: Move to fresh air, seek medical advice if symptoms persist.
Skin: Wash with soap and water; remove contaminated clothing.
Eyes: Rinse cautiously with water for several minutes; seek medical attention.
Ingestion: Rinse mouth; do not induce vomiting; seek medical help.
Spills/Waste: Collect solid with minimal dust generation. Dispose of via licensed chemical waste contractor in accordance with local regulations.
Storage (item-specific): Protected from light, store at −20 °C, argon charged. Shipments: Ice chest + ice pads.
Solvent Selection
Applicability: High—TOTU is deployed in polar organic media for carboxylate activation and amide bond formation.
General solvent guidance (literature/practice):
Preferred solvents (polar aprotic):
DMF, NMP, DMAc: excellent solubility of both reagent and typical peptide substrates; widely used in SPPS.
DCM and mixtures (DCM/DMF): useful for resin swelling (e.g., polystyrene-based resins) while maintaining solubility of reagents.
Acetonitrile: suitable for solution-phase couplings of small molecules; sometimes mixed with DMF to improve substrate solubility.
Protic solvents: Avoid during activation/coupling (MeOH, EtOH, water) as they quench activated species and reduce coupling efficiency.
Green(er) solvent choices (see also Green Alternatives):
N-butylpyrrolidone (NBP), propylene carbonate (PC), 2-MeTHF, CPME, and EtOAc have been reported as partial or full substitutes for DMF/DCM in specific peptide workflows.
Practical selection tips:
SPPS on PS-based resins: Start with DCM for resin swelling, then switch to DMF/NMP for coupling with TOTU + base (e.g., DIPEA). For PEG-based resins, purely DMF/NMP is often sufficient.
Solubility constraints: For hydrophobic sequences, include small percentages of DCM or ACN to maintain homogeneous mixtures.
Temperature: Room temperature is typical; if heating (e.g., 30–50 °C) is applied to speed sluggish couplings, reassess solvent stability and base strength to limit side reactions.
Storage and Reconstitution
Item-specific storage conditions:
Store at −20 °C, protected from light, under argon (argon charged).
Shipped in an ice chest with ice pads.
Handling and reconstitution (general best practices):
Allow container to equilibrate to room temperature in a desiccator before opening to prevent moisture condensation.
Open and dispense under inert atmosphere when possible (e.g., glovebox or dry nitrogen/argon stream). Reseal promptly.
Prepare stock solutions in anhydrous DMF, NMP, DMAc, DCM, or acetonitrile. Typical concentrations for SPPS are 0.2–0.6 M; for solution-phase, adjust to substrate solubility.
Filter stock solutions (0.2 μm PTFE) if using on automated synthesizers to prevent particulates from fouling lines/valves.
Stability of solutions: Use freshly prepared solutions for best performance. If storage is necessary, keep under inert gas at −20 to 0 °C, protected from light; verify activity before critical use. Exact shelf-life is not specified for this item; refer to CoA/Spec Sheet.
Avoid repeated freeze–thaw of solutions; aliquot solids or solutions for single-use where possible.
Disposal: Treat unused solids/solutions and washings as hazardous organic waste according to institutional and local regulations.
Research use note: For research use only.
Structure and Identity
TOTU is a uronium-type peptide coupling reagent widely used for forming amide bonds in solution- and solid-phase peptide synthesis (SPPS).
SKU: E102847
Product name: TOTU
CAS: 136849-72-4 (item-specific)
PubChem CID: 2733286 (item-specific)
InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
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 features (general/literature description):
Uronium cation bearing a tetramethylurea-derived core activated as an O-acyloxy species.
O-activated leaving group is a 1,2,4-triazolyl (triazol-1-yloxy) moiety, enabling efficient acyl transfer.
Counterion typically a tetrafluoroborate (BF4−) in commercial materials; consult the CoA for this specific lot.
Functionally, it converts carboxylic acids to reactive O-acyluronium intermediates in situ, facilitating coupling with amines to form amides/peptides.
2D structural description (general):
Central uronium fragment [NMe2–C(=NMe2)–O–(leaving group)] carries a positive charge delocalized over the urea nitrogens; paired with a non-nucleophilic anion (e.g., BF4−). The leaving group ring is a 1,2,4-triazole connected via an O–N linkage (triazolyl-oxy). No stereocenters present.
Synthetic Utility
Core reactivity:
Converts carboxylic acids into reactive O-acyluronium intermediates, enabling rapid coupling with amines to form amides/peptides.
Triazolyl leaving group offers a balance of reactivity and stability, often affording clean couplings with reduced discoloration compared to benzotriazole analogs.
Applications (literature/practice):
SPPS: Efficient coupling of Fmoc-protected amino acids to resin-bound amines (primary and many secondary amines). Useful for hindered residues (Val, Ile, tBu-protected derivatives) and β-branched sites.
Solution-phase amide formation: Small-molecule amidations, lactamizations (intramolecular variants), and fragment couplings.
Mixed anhydride alternatives: Provides a single-step, in situ activation route avoiding external anhydrides.
Minimizing epimerization: Fast acyl transfer and reduced oxazolone lifetime can lower epimerization versus carbodiimide-only protocols; consider additives and temperature control for sensitive α-stereocenters.
Retrosynthetic value:
Facilitates late-stage union of acid and amine fragments where functional group tolerance is required (esters, nitriles, halides generally tolerated). Alcohols and thiols should be protected or excluded to prevent side acylation.
Byproducts and cleanup:
Generates triazole and substituted urea derivatives; typically removed by resin washes (SPPS) or aqueous workup and chromatography (solution-phase). Optimize base and stoichiometry to limit N-acylurea formation.
Target Specificity
Not applicable. TOTU is a small-molecule coupling reagent and does not possess biological target specificity, antigen recognition, or isotype characteristics. This section pertains to biologics/antibodies, which is not relevant here.
Perguntas frequentes
What is the purity of this product?
This product is supplied at ≥98% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.
How should this product be stored?
Store at ?20 °C, protected from light, under argon. It is supplied under an argon blanket; reseal under inert gas after each use.
How is this product shipped?
This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.
What are the CAS number, molecular formula and molecular weight?
The CAS Number is 136849-72-4, the molecular formula is C10H17BF4N4O3, and the molecular weight is 328.07 g/mol. InChIKey FPQVGDGSRVMNMR-UHFFFAOYSA-N.
What documentation is provided?
Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.
Usamos cookies para garantir o funcionamento adequado do site e, quando permitido, para melhorar a sua experiência. Você pode gerenciar suas preferências a qualquer momento nas Configurações. Saiba mais em nossa Política de Cookies.
Deseja que lhe enviemos uma mensagem quando tivermos descontos disponíveis?
Lembrar-me mais tarde
Obrigado! Por favor, verifique a sua caixa de entrada de e-mail para confirmar.
Products are supplied to verified businesses, institutions, and qualified professionals for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
K2122118