Z-Trp-Bt - ≥95% , CAS No.850232-59-6

CAS: 850232-59-6 Cat. No.: Z467434 Peso molecolare: 439.47 Numero EC: 687-159-5

GRADE & PURITY ≥95%

Synonyms

(S)-N-Z-1-Benzotriazolylcarbonyl-2-(3-indolyl)ethylamine, (S)-Benzyl (1-(1H-benzo[d][1,2,3]triazol-1-yl)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)carbamate

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Panoramica

Description

Benzotriazole amino acids, or aminoacylbenzotriazolides, are versatile reagents for synthesizing peptides as well as their mimetics and conjugates. Benzotriazole amino acids have been used for the preparation of diverse derivatives including:Polypeptidal benzotriazolidesPeptidomimetics, such as aminoxypeptides, depsipeptides and heterocyclic peptidomimeticsTagged peptides and peptidomimetics, particularly those with fluorescent labelsN, O, S, and C linked peptide conjugates

Specifications

Sinonimi

(S)-N-Z-1-Benzotriazolylcarbonyl-2-(3-indolyl)ethylamine, (S)-Benzyl (1-(1H-benzo[d][1,2,3]triazol-1-yl)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)carbamate

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Store at -20°C

Spedito in

Ice chest + Ice pads

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Purezza

≥95%

Nomi e identificatori

WGK Germania

3

Peso molecolare

439.47

Application Protocols

No immunoassay or cell-based application protocols apply to this small-molecule building block. For synthetic use, see Reaction Conditions and Synthetic Utility sections for general coupling guidance. Any detailed procedure should be optimized per substrate and verified by small-scale trials.

Biological Roles

This product is a protected and activated derivative intended for chemical synthesis; it does not have a direct biological role.

General context (literature):

• Tryptophan is an essential amino acid featuring an indole side chain that is often involved in protein–protein interactions, π–π stacking, and fluorescence signaling in proteins (emission ~350 nm when excited near 280 nm, depending on environment).
• Z-protection (CBz) and OBt activation are synthetic modifications used to control reactivity during peptide assembly; they mask the native amine and activate the carboxylate for amide bond formation, respectively.
• In biological systems, free tryptophan participates in the shikimate/tryptophan biosynthetic pathway (in microbes/plants) and feeds into the kynurenine and serotonin/melatonin pathways in animals. These pathways are not applicable to the protected synthetic intermediate offered here.

Conclusion: Use of Z-Trp-Bt should be limited to research and laboratory synthesis of peptides and amides; it is not intended for cellular assays without deprotection/processing and validation.

Buffer Applications

Not typically applicable. Z-Trp-Bt is a moisture-sensitive activated ester used for chemical coupling, not a buffering agent. For peptide couplings, anhydrous organic solvents (e.g., DMF, NMP, DCM) are preferred over aqueous buffers to prevent hydrolysis. If aqueous work is required downstream, perform the coupling in organic media, then quench and transfer to buffered systems after purification of the amide product.

Green Alternatives

Greener choices can be made at both solvent and coupling-chemistry levels (literature/general guidance):

• Solvent substitutions:

  • Replace DCM with 2-Methyltetrahydrofuran (2-MeTHF) or cyclopentyl methyl ether (CPME) where solubility permits.
  • Consider N-Butylpyrrolidone (NBP) or propylene carbonate as alternatives to DMF/NMP in some peptide couplings, mindful of viscosity and workup.

• Activation alternatives to OBt esters:

  • Use Oxyma-based couplings (e.g., EDCI + OxymaPure, COMU) to reduce reliance on benzotriazole derivatives while maintaining high coupling efficiency and low racemization.
  • Employ mixed anhydrides or acid fluorides formed in situ under milder/safer profiles in specific cases.

Comparison (general):

• OBt ester vs. Oxyma-assisted EDCI
  • Safety: Oxyma systems avoid benzotriazole byproducts; reduced energetic risk profile.
  • Waste: EDCI urea byproducts are water-soluble, easing workup; OBt generates benzotriazole.
  • Performance: Both can deliver high conversions; choice depends on substrate solubility, epimerization risk, and scale.

Caveats:

• Solubility and kinetics may differ in greener solvents; small-scale trials are recommended.
• Ensure compatibility of amine partners and protecting groups with the chosen green solvent and activation system.

Pharmaceutical Uses

• Role: Research intermediate/building block in the synthesis of peptide APIs and peptidomimetics; facilitates the introduction of Nα-Z-protected tryptophan moieties during fragment coupling (general/literature context). Not for human or veterinary use.
• Formulation/excipient status: Not an excipient; not intended for direct inclusion in dosage forms.
• Regulatory considerations (general): When used in GMP environments as a starting material or intermediate, suppliers typically provide documentation on identity, purity profile, residual solvents, and impurity limits. This item’s specific grade/purity is Not specified for this item; refer to CoA/Spec Sheet.
• Process utility:
  • Enables convergent assembly of peptide fragments, potentially improving step economy versus in situ activation.
  • Can reduce exposure to carbodiimide coupling agents during specific steps, simplifying impurity control strategies.
• Handling in process development:
  • Establish robust controls for moisture and temperature to maintain assay.
  • Define hold times for solutions in DMF/NMP/DCM; study hydrolysis kinetics under intended conditions.
  • Validate removal of benzotriazole byproduct during workup/purification.

Research Use Note: For research use only.

Physical Properties

Item-specific physico-chemical specifications are not provided in the Product Data.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point, boiling point, density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (general/literature guidance for Z-protected amino acid OBt esters):
  • Typically soluble in polar aprotic organic solvents (e.g., DMF, NMP, DCM, THF, acetonitrile) and in DMSO; limited solubility in water and nonpolar alkanes.
  • Solubility can be improved by gentle warming and sonication; always use anhydrous solvents to prevent hydrolysis.
• pKa/logP: Not specified for this item; refer to CoA/Spec Sheet. (Note: protected/activated esters display reduced ionizability vs. the parent amino acid.)
• Hygroscopicity/hydrolytic sensitivity (general): Activated OBt esters are moisture sensitive and may hydrolyze to the parent acid; handle under dry conditions and minimize exposure to ambient humidity.
• Optical rotation: Not specified for this item; refer to CoA/Spec Sheet.

All numerical property values should be confirmed on the CoA/Spec Sheet for this specific lot.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• What the designation implies (general guidance): For peptide building blocks and activated esters, higher grades typically ensure low residual solvents, tight control of diastereomeric purity (L-stereochemistry retention), and low levels of hydrolysis or decomposition products (e.g., benzotriazole, Z-Trp acid). Chromatographic purity is commonly reported by HPLC along with NMR identity.
• Stabilizers: None specified for this item; refer to CoA/Spec Sheet. In general, moisture exclusion (desiccant, inert gas) functions as the principal “stabilization” strategy for OBt esters.
• Batch-specific controls usually include:
  • Identity: 1H/13C NMR, MS; sometimes IR and elemental analysis.
  • Purity: HPLC assay, with reporting of related substances such as Z-Trp and benzotriazole.
  • Optical purity: where applicable, chiral HPLC or optical rotation to confirm L-configuration.
• Recommendation: Verify certificate data (assay, water content, residual solvents, and stereochemical integrity) on the CoA/Spec Sheet before critical applications in peptide synthesis.

Reaction and Applications

• Primary application (literature/general): Z-Trp-Bt functions as a pre-activated ester of Nα-benzyloxycarbonyl-L-tryptophan for direct amide bond formation with amines. It enables solution- or solid-phase peptide elongation without on-site activation reagents.
• Advantages:
  • Operational simplicity: Mix-and-stir coupling under mild conditions.
  • Reduced exposure to carbodiimides; mitigates urea byproduct handling.
  • Often lower racemization risk versus acid chlorides or anhydrides when conditions are controlled.
• Typical use cases:
  • N-terminal capping of peptide fragments with Z-Trp.
  • Fragment condensation where the amine-bearing partner is base-labile.
  • Installation of Trp units into peptidomimetics and small-molecule amide libraries.
• Practical tips:
  • Employ anhydrous solvent (DMF, NMP, DCM) and a non-nucleophilic base (e.g., DIPEA, collidine) as needed to neutralize any acidic byproducts and maintain amine nucleophilicity.
  • Maintain 0–25°C to limit racemization at the α-center; brief pre-cooling can be helpful for particularly base-sensitive substrates.
  • Use slight excess of the amine (1.1–1.5 equiv) or of the active ester, depending on purification preference.
  • Monitor by TLC/HPLC; benzotriazole release can be tracked as a diagnostic byproduct.
• Limitations/considerations:
  • Moisture sensitivity—hydrolysis reduces effective concentration.
  • Indole side chain of Trp can participate in side reactions under strongly electrophilic/oxidizing conditions; protect from strong acids and oxidants.
  • OBt-related safety: handle away from heat sources; avoid grinding or friction with large quantities (general precaution for energetic benzotriazole derivatives).

Reaction Conditions

General literature guidance for coupling with Z-protected amino acid OBt esters (optimize per substrate):

• Solvent: Anhydrous DMF, NMP, or DCM; mixtures (e.g., DCM/DMF 1:1) often balance solubility and reactivity.
• Base: 1.0–2.0 equiv of a non-nucleophilic tertiary amine (DIPEA, Hunig’s base) to deprotonate amine nucleophiles and neutralize any acidic byproducts. In some cases, coupling proceeds without added base when the amine is sufficiently nucleophilic.
• Stoichiometry: 1.0 equiv Z-Trp-Bt to 1.1–1.5 equiv amine (or invert the excess to drive to completion depending on purification strategy).
• Temperature: 0–25°C to limit epimerization; difficult substrates may benefit from brief cooling (0–5°C) at initiation, then warming to RT.
• Time: 0.5–6 h typical; monitor by TLC/HPLC/LC–MS.
• Atmosphere: Inert (N2/Ar) recommended; rigorously dry glassware and solvents.
• Additives: Catalytic DMAP can accelerate reactions with less nucleophilic amines but may increase side reactions; use judiciously and at low loadings.
• Workup: Quench into dilute aqueous bicarbonate or brine; extract with DCM/EtOAc; wash to remove benzotriazole; dry and concentrate. Purify by column chromatography or preparative HPLC as needed.
• Expected outcomes: High conversions are common with primary aliphatic amines; anilines and hindered amines may require longer times or elevated temperature (still within racemization-safe limits).
• Epimerization control: Minimize base contact time; avoid strong bases; maintain low temperature; rapid isolation of product recommended.

Safety and Handling

• GHS classification, signal word, hazard statements, pictograms: Not specified for this item; refer to the SDS for authoritative safety information.
• General hazards (literature/general): Activated benzotriazolyl esters are irritants and can be harmful if inhaled, ingested, or absorbed through skin. They may cause eye, skin, and respiratory irritation. Dust or fine particulate should be minimized.
• PPE: Lab coat, safety glasses or goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of dust or solvent vapors during solution handling.
• Handling precautions:
  • Avoid moisture; hydrolysis yields the corresponding acid and benzotriazole, reducing coupling efficiency.
  • Avoid strong bases and prolonged basic conditions that may promote racemization or decomposition.
  • Prevent contact with strong oxidizers and strong acids; avoid heat and direct sunlight.
• First aid (overview; consult SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical attention as needed.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill/cleanup: Avoid dust, contain with inert absorbent, collect for disposal following institutional and local regulations.
• Waste: Dispose according to local/regional regulations; avoid release to the environment.

Solvent Selection

General (literature) solvent behavior for Z-protected amino acid benzotriazolyl esters:

• Polarity/miscibility:
  • Good solubility in polar aprotic solvents: DMF, NMP, DCM, THF, acetonitrile, DMSO.
  • Limited to poor solubility in water and aliphatic hydrocarbons (hexanes, heptane).
• Typical use scenarios:
  • Peptide couplings with amines in DMF or NMP for homogeneous reaction media.
  • DCM or DCM/DMF mixtures for improved handling with base-sensitive partners.
  • DMSO reserved for challenging solubility cases; be mindful of downstream removal.
• Selection guidance:
  • Choose DMF/NMP for solid-phase or solution-phase peptide couplings where amine nucleophiles are present with a mild base (e.g., DIPEA) to capture acid byproducts.
  • Use DCM or 2-MeTHF when lower polarity benefits selectivity or downstream workup.
• Dielectric constants (literature, typical): DMF ~36.7, NMP ~32, DCM ~9.1, THF ~7.6, acetonitrile ~36; these support ion-pair stabilization during amide formation.
• Dryness is critical: Use anhydrous, oxygen/moisture-free solvents; pre-dry glassware and maintain inert atmosphere to limit hydrolysis and preserve coupling efficiency.
• Comparative note: Versus acid chlorides, OBt esters generally offer better chemoselectivity and reduced side reactions, allowing broader solvent choices.

Storage and Reconstitution

• Storage conditions (item-specific): Store at -20°C. Shipped in an ice chest with ice pads.
• Packaging/handling: Keep tightly closed under inert gas with a desiccant. Minimize headspace moisture and repeated vial openings. Protect from light and heat.
• Stability considerations (general for OBt esters): Sensitive to moisture; gradual hydrolysis may occur even at low temperatures if not well sealed. Avoid prolonged storage in solution; prepare solutions fresh.
• Reconstitution/dissolution (general guidance):
  • Use anhydrous solvents such as DMF, NMP, DCM, THF, or DMSO. Start with a small volume and dilute to the desired concentration after complete dissolution.
  • If needed, gentle warming (≤30–35°C) and brief sonication can aid dissolution; avoid excessive heat.
• Solution handling: Work under dry nitrogen/argon. For multi-use, prepare aliquots and store at -20°C; bring to room temperature before opening to prevent moisture condensation. Discard solutions showing signs of hydrolysis (new acid peak by HPLC, reduced assay).
• Freeze–thaw: Avoid repeated freeze–thaw cycles; aliquot to single-use portions.
• Shelf life: Not specified for this item; refer to CoA/Spec Sheet.
• Safety: Consult the SDS for detailed handling and emergency measures. Research use only.

Structure and Identity

• Item name: Z-Trp-Bt (commonly interpreted in peptide chemistry as a benzyloxycarbonyl-protected tryptophan activated as a benzotriazolyl ester; general description based on literature conventions)
• CAS: 850232-59-6
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• Structural features (general/literature):
  • Contains an N-terminal benzyloxycarbonyl (Z/CBz) protecting group on tryptophan’s amino functionality.
  • Carboxyl group is converted to an activated benzotriazol-1-yl (OBt) ester, enabling direct coupling to amines.
  • Retains the L-tryptophan side chain bearing an indole ring; no stereocenter is created in the activation step, so the α-stereocenter of Trp is preserved if handled under racemization-minimizing conditions.
  • 2D description in words: a benzyloxyl carbonyl carbamate linked to the α-amino of tryptophan; the α-carboxyl is esterified to a benzotriazolyl leaving group; the β-position bears an indole-containing side chain.

Synthetic Utility

• Functional group set (general): Nα-Z-protected L-tryptophan activated as a benzotriazol-1-yl ester provides an electrophilic carboxyl component for amide bond formation with amines, anilines, and amino acid residues on resins (solid-phase) or in solution.
• Selectivity: Preferential acylation of primary aliphatic amines > secondary aliphatic amines > anilines; phenols/thiols react more slowly under comparable conditions. The indole side chain is generally non-nucleophilic under coupling conditions but is acid/oxidation sensitive.
• Named-reaction context: Falls under the umbrella of “active ester couplings” related to HONB/HOBt methodologies; mechanistically akin to carbodiimide-mediated couplings but with a pre-formed leaving group.
• Retrosynthetic value: Replaces the need for in situ activation (e.g., DIC/HOBt) by delivering an isolable, shelf-stable enough acyl donor for rapid couplings and fragment condensations.
• Downstream manipulations:
  • After coupling, Z protection can be removed via catalytic hydrogenolysis (H2, Pd/C) under conditions that preserve sensitive residues; alternative deprotection strategies exist depending on substrate tolerance.
  • The newly formed amide can enter further peptide elongation or global deprotection schemes.
• Limitations: Hydrolysis competes with coupling in moist environments; prolonged basic conditions risk epimerization at the α-carbon. Employ low temperatures, short contact times with base, and rapid workups.

Target Specificity

Not applicable. This product is a small-molecule synthetic intermediate, not a biological affinity reagent. No antigen/epitope, species reactivity, clone, or isotype data apply.