THP-PEG1-Boc , CAS No.T1445568

CAS: T1445568 Cat. No.: T1445568 Formula: C₁₃H₂₄O₅ Molecular Weight: 260.33

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

THP-PEG1-Boc is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

Specifications

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Names and Identifiers

• Molecular Weight: 260.33

Application Protocols

No tested biological application protocols (e.g., WB, IHC, IF, FC) are applicable or provided for this small-molecule linker. For chemical use, general workflows include:

• Boc deprotection protocol (general)

  • Dissolve substrate in DCM (0.05–0.2 M). Add TFA to 20–50% v/v at 0–25°C. Stir 10–30 min. Concentrate under reduced pressure. Neutralize residue with iPr2NEt in DCM, filter through a plug of silica or SCX resin, and elute product.

• THP deprotection protocol (general)

  • Dissolve substrate in MeOH (0.05–0.2 M). Add PPTS (5–10 mol%). Stir at rt for 1–3 h. Quench with sat. NaHCO3, remove solvent, extract with EtOAc, dry, and purify.

• Post-deprotection coupling (general)

  • For amide formation, dissolve amine and acid partner in DMF (0.05–0.1 M), add HATU (1.1 eq) and iPr2NEt (2 eq), stir 1–2 h at rt, then work up and purify.

These are literature-style general methods and not validated for this specific item. Adjust stoichiometry, temperature, and solvent based on substrate behavior and analytical monitoring.

Biological Roles

Item-specific biological data are not provided, and this product is designated for research use only. The following context reflects general knowledge about PEG-based linkers and protecting groups in chemical biology workflows (not clinical claims):

• PEG spacers (general)

  • Short PEG units (e.g., PEG1) increase hydrophilicity and flexibility, often improving solubility of small conjugates in organic media and moderating nonspecific interactions in biochemical assays.

• Protecting-group utility in bioconjugation (general)

  • Boc-protected amines and THP-protected alcohols allow stepwise unveiling of nucleophiles, enabling controlled assembly of probes, affinity tags, or surface modifiers under conditions compatible with sensitive functional groups elsewhere in the molecule.

• No intrinsic bioactivity implied

  • THP-PEG1-Boc itself is not intended to exert a specific biological function; it serves as a synthetic intermediate/linker used upstream of biological testing.

• Metabolic/enzymatic considerations (general)

  • PEG linkers are typically resistant to many enzymes; however, once deprotected and incorporated into final structures, metabolism and clearance are determined by the full conjugate, not the isolated linker.

Researchers should validate compatibility with their biological systems after final conjugation and purification. This product is not intended for therapeutic or diagnostic use.

Buffer Applications

This compound is a protected, organic linker and is not a buffering agent. It is not typically used to prepare aqueous buffer systems or to control pH directly.

• Practical guidance (general)
  • If aqueous handling is required after conjugation, select buffers that do not cleave acid-labile groups (avoid strong acids). For operations requiring retention of THP/Boc protections, maintain neutral pH and minimize exposure to aqueous media.
  • For deprotection steps conducted in organic media, buffers are generally not involved; quenching and neutralization can be achieved with non-aqueous bases or solid-supported scavengers.

For buffer formulation details related to your final target conjugates, refer to the chemistry of the deprotected functional groups (e.g., amines in phosphate or HEPES buffers following Boc removal), not to this protected intermediate.

Green Alternatives

Greener practice with THP-PEG1-Boc centers on solvent and reagent selection, since the protecting groups themselves are defined. Below are general, literature-based considerations.

• Solvent choices (comparative, general)

  • DCM replacement: Ethyl acetate or 2-MeTHF can substitute in many workups/reactions; heptane/EtOAc mixtures aid crystallizations and extractions.
  • THF alternatives: 2-MeTHF or CPME offer improved safety/greenness and reduced peroxide concerns; both support many coupling and protection steps.
  • Polar aprotic: Replace DMF/NMP with safer options where possible (e.g., MeCN, propylene carbonate) recognizing tradeoffs in solubility and reaction rates.

• Acid selection for deprotection (general)

  • Boc removal: Use lower percentages of TFA in a greener solvent (EtOAc, MeCN) with efficient mixing; recover and neutralize acids via trapping on solid bases.
  • THP cleavage: Employ catalytic, less hazardous acids (e.g., PPTS) in alcohol solvents instead of strong mineral acids; ethanol can substitute for methanol when feasible.

• Workup/waste minimization

  • Inline scavengers and solid-supported acids/bases reduce aqueous waste.
  • Telescoping deprotection/coupling limits intermediate isolations and solvent usage.

• Tradeoffs

  • Greener solvents may alter solubility; reaction rates or selectivity can change. Conduct small-scale DoE to re-optimize conditions.

Summary table (general):

• Conventional: DCM, THF, DMF, TFA/DCM.
• Greener leaning: EtOAc or 2-MeTHF for DCM; 2-MeTHF/CPME for THF; MeCN/propylene carbonate for DMF; catalytic PPTS in EtOH for THP deprotection; minimized TFA load in EtOAc/MeCN for Boc removal.

Adopt process safety reviews to balance EHS benefits with performance.

Pharmaceutical Uses

No pharmacopeial status or excipient designation is provided for this item. This product is intended for research use only and is typically employed as a synthetic intermediate/linker rather than as a formulated component.

• General process/R&D context (non-clinical)

  • Heterobifunctional PEG linkers are often explored during lead optimization and probe development to modulate physicochemical properties of small molecules and to introduce spacing between pharmacophores in research settings.
  • The Boc/THP protections enable orthogonal synthetic routes that may be used during the preparation of candidate molecules prior to any formulation studies.

• Manufacturing considerations (general)

  • If used upstream in process development, control of residual solvents, moisture, and acid/base residues is important to ensure robust downstream reactions and crystallizations.
  • Any application in GMP settings would require independent qualification and specification setting; none are provided here.

No therapeutic claims are made or implied. For any regulated use, consult appropriate guidelines and establish full specifications and controls based on your internal quality systems.

Physical Properties

Item-specific physical constants were not provided for this product. Please consult the CoA/Spec Sheet for definitive specifications.

• Item-specific status

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Density, refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

• General expectations for related compounds (literature/general guidance)

  • Physical state: Heterobifunctional PEG1 linkers are commonly low-melting solids or viscous oils at ambient temperature, depending on exact end-groups.
  • Solubility: Typically soluble in common organic solvents (DCM, THF, EtOAc, MeOH, ACN) and partially miscible with water due to PEG content; Boc and THP termini favor organic phases.
  • Polarity: Moderate polarity (due to ether oxygens and carbamate) with limited volatility; logP is formulation-dependent and not universally tabulated for such specific linkers.
  • Thermal behavior: Boc and THP groups decompose/cleave under acid and heat; avoid prolonged exposure to strong acids or elevated temperatures during storage/handling.

• Practical notes (general)

  • Hygroscopicity: PEG-bearing molecules can be mildly hygroscopic; dispense quickly under dry atmosphere to maintain material integrity.
  • Solution stability: More stable in anhydrous, neutral organic solvents; avoid acidic media if protection integrity must be preserved.

All numeric values for this specific item are not specified; verify properties with the product’s CoA or SDS prior to critical use.

Quality and Grades

• Item-specific quality information

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

• How to interpret grades (general guidance)

  • Research/technical grade: Suitable for general synthesis and development work; impurity profiles may not be optimized for trace-level analytics.
  • High-purity or HPLC grade (if applicable on CoA): Typically features low non-volatile residue and low UV-absorbing impurities, supporting use in chromatographic workflows or sensitive coupling steps.
  • Bioconjugation grade (if specified): May indicate tighter control over residual solvents, heavy metals, and moisture—important for downstream applications on sensitive biomolecules.

• Practical quality considerations for THP-PEG1-Boc (general)

  • Moisture content: Water can accelerate THP/Boc lability; Karl Fischer values (if provided on CoA) are a useful indicator for handling rigor.
  • Residual acids/bases: Trace acids catalyze THP cleavage; trace amines/bases can promote carbamate transesterification. Review residuals on CoA.
  • Metals and peroxides: PEG-containing materials are not typical peroxide formers like ethers such as THF, but peroxide content and metal limits—if critical for your process—should be checked on the CoA.

Always rely on the batch-specific CoA for definitive purity, assay, and impurity profiles. Adjust purification and handling strategies accordingly.

Reaction and Applications

Without item-specific application notes, the following guidance reflects common uses of heterobifunctional PEG linkers bearing THP and Boc protections (literature/general):

• Protection/deprotection strategies

  • THP group: Protects alcohols as acetals; removable under mild acid (e.g., catalytic PPTS in MeOH or aq. AcOH). Useful for masking hydroxyl reactivity during carbamate formation or coupling steps.
  • Boc group: Masks primary/secondary amines as tert-butyl carbamates; cleaved rapidly by TFA in DCM or HCl in dioxane, typically at 0–25°C.

• Spacer utility

  • PEG1 unit: Provides minimal yet effective spacing to reduce steric congestion and improve solubility in organic media during stepwise synthesis.

• Representative workflows

  • Sequential unmasking: Choose conditions to selectively remove one protecting group while leaving the other relatively intact (e.g., mild, non-nucleophilic acid to remove Boc rapidly; buffered acid/alcohol for more controlled THP cleavage). Kinetic control and stoichiometry are critical.
  • Conjugation: After deprotection, liberated hydroxyl or amine can be converted to activated esters, carbonates, carbamates, or amide linkages for attachment to small molecules, polymers, or surfaces.

• Practical tips

  • Dry conditions are important to prevent premature THP hydrolysis.
  • Scavenge acids/bases after deprotection (e.g., with solid-supported reagents) to limit side reactions.
  • Monitor by TLC or LC–MS; Boc removal is typically evident by loss of tert-butyl cation fragment (m/z 57) in MS.

This product is intended for research use only; suitability for specific transformations should be verified experimentally.

Reaction Conditions

The following are general, literature-based conditions relevant to compounds bearing THP and Boc protecting groups. Optimize for your substrate and scale.

• Boc deprotection (general)

  • Reagent/solvent: 20–100% TFA in DCM or MeCN; or 3–4 M HCl in dioxane.
  • Temperature/time: 0–25°C, 5–60 min for many substrates.
  • Workup: Evaporate volatiles; neutralize with a suitable base (e.g., iPr2NEt) or capture acid on solid-supported carbonate; purify by chromatography.

• THP deprotection (general)

  • Catalyst: PPTS (5–10 mol%) or p-TsOH (cat.) in MeOH/EtOH or acetone/H2O.
  • Temperature/time: 0–25°C, 0.5–6 h depending on substitution and medium.
  • Notes: Alcoholic solvents aid formation of the liberated alcohol; buffer strength to avoid concurrent Boc loss if needed (use milder acids and lower temperature).

• Coupling after deprotection (general)

  • Amide formation: HATU/HOAt or EDCI/HOBt in DMF/DCM with iPr2NEt; 0–25°C, 1–4 h; typical yields for unhindered partners 70–95% (literature ranges).
  • Carbonate/carbamate formation: p-NPC or CDI activation in DCM/THF; 0–25°C, 1–3 h.

• Analytical monitoring

  • LC–MS for rapid assessment (look for tert-butyl cation at m/z 57 for Boc loss; mass decrease consistent with THP removal).
  • NMR: Disappearance of Boc tert-butyl singlet (~1.4 ppm) and THP methylene multiplets (3.3–4.0 ppm) are indicative (solvent-dependent).

These conditions are typical references and not item-specific specifications. Pilot on millimole scale to refine stoichiometry and times.

Safety and Handling

Safety information specific to this item (GHS classification, hazard statements, pictograms) was not provided. Always review the product SDS for authoritative guidance.

• Item-specific safety data

  • Signal word: Not specified for this item; refer to SDS.
  • H-statements: Not specified for this item; refer to SDS.
  • GHS classification/pictograms: Not specified for this item; refer to SDS.
  • Storage: Store at −20°C (per Product Data). Shipped in ice chest with ice pads to maintain cold chain.

• General handling guidance (for PEGylated protecting-group reagents; literature/general)

  • PPE: Use appropriate laboratory PPE (lab coat, safety glasses, disposable nitrile gloves). Handle in a fume hood to avoid inhalation of dusts/vapors.
  • Incompatibilities: Avoid strong acids if protection must be retained (both THP and Boc are acid-labile). Strong bases and nucleophiles may induce side reactions at the carbamate or acetal under forcing conditions.
  • Stability considerations: Moisture and protic acids catalyze THP acetal cleavage; TFA and HCl rapidly remove Boc. Keep containers tightly closed under dry, inert atmosphere when possible.
  • First aid (overview; consult SDS): In case of skin/eye contact, rinse with water for at least 15 minutes and remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; seek medical attention for any exposure concerns.
  • Fire safety: Organic carbamates/ethers are combustible. Use CO2, dry chemical, or foam to extinguish. Avoid high-temperature decomposition.

This product is for research use only (per Product Data). Defer to SDS and institutional protocols for risk assessment.

Solvent Selection

THP-PEG1-Boc behaves as a moderately polar, organic-soluble small-molecule linker. Absent item-specific solubility data, select solvents based on general behavior of PEGylated, Boc/THP-protected species.

• Polarity/miscibility (general/literature)

  • Good solubility: DCM, CHCl3, THF, EtOAc, MeOH, ACN, DMF, DMSO.
  • Limited solubility: Aliphatic hydrocarbons (hexanes, heptane), unless co-solvent is used.
  • Aqueous media: Typically poor to moderate solubility; PEG1 is short and does not confer strong water solubility.

• Selection by task

  • Protection maintenance: Use neutral, anhydrous solvents (DCM, THF, toluene, EtOAc). Avoid acids if THP/Boc must remain intact.
  • THP deprotection: Alcoholic solvents (MeOH, EtOH) with catalytic acid (e.g., PPTS) often effective (literature).
  • Boc deprotection: DCM or MeCN with TFA; or dioxane with HCl (literature).
  • Coupling/activation: Polar aprotic solvents (DMF, DCM, MeCN) support carbodiimide or NHS-ester chemistry on deprotected functionalities.

• Comparison notes (general)

  • DCM vs THF: DCM often dissolves Boc/THP species more readily and facilitates acid-mediated steps; THF is preferred for base-mediated couplings but ensure anhydrous conditions.
  • DMF/DMSO: Maximize solubility for high-loading reactions; consider downstream removal and potential base-catalyzed side reactions.

Confirm solubility and stability experimentally on small scale, as actual behavior depends on the precise structure and batch-specific attributes.

Storage and Reconstitution

• Item-specific storage/shipping

  • Storage conditions: Store at −20°C (per Product Data).
  • Shipped in: Ice chest with ice pads (per Product Data) to maintain low temperature during transit.

• General handling and reconstitution guidance

  • Atmosphere: Handle quickly under dry air or inert gas to minimize moisture exposure; both THP and Boc protections are acid-labile, and adventitious moisture/acids can reduce integrity over time.
  • Container: Keep tightly closed in the original amber vial or transfer to moisture-barrier containers with desiccant.
  • Reconstitution: Prepare stock solutions in anhydrous organic solvents compatible with downstream chemistry (e.g., DCM, THF, MeCN, DMF). Filter if particulates are present.
  • Solution stability: Best maintained at 0–5°C for short term or −20°C for longer term in dry, neutral solvents. Avoid acidic media if protecting groups must be preserved. Specific stability data for this item are not specified; verify by LC–MS/NMR.
  • Freeze–thaw: If storing solutions at subzero temperatures, aliquot to avoid repeated freeze–thaw cycles, which may introduce moisture and promote deprotection.

• Retest/expiration

  • Not specified for this item; refer to CoA/Spec Sheet. As a best practice, check purity by LC–MS or NMR prior to critical use, especially after extended storage.

For research use only. Always consult the SDS for detailed handling and disposal instructions.

Structure and Identity

Brief overview: THP-PEG1-Boc is a heterobifunctional, PEG-based protecting/linker reagent featuring a tetrahydropyranyl (THP) protecting group on one terminus and a tert-butyloxycarbonyl (Boc) carbamate on the other, separated by a short ethylene glycol spacer (PEG1). This makes it useful for orthogonal protection and stepwise assembly in organic and bioconjugation workflows.

• Item-specific data (from Product Data)

  • SKU: T1445568
  • Product name: THP-PEG1-Boc
  • CAS: T1445568
  • 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 description)

  • Functional groups: THP acetal-protected alcohol; Boc-protected amine (carbamate); internal ether linkage (–O–CH2–CH2–O–) characteristic of PEG1.
  • Topology: Linear, heterobifunctional small-molecule linker with one oxygen-rich PEG unit conferring polarity and solubility in organic media.
  • Orthogonality: Both THP and Boc are typically acid-labile protecting groups; deprotection kinetics and conditions can be tuned (e.g., PPTS/MeOH for THP; TFA/DCM for Boc) to achieve sequential unmasking when needed.
  • 2D description: A six-membered saturated ring (tetrahydropyran) tethered via an ether to an ethylene glycol unit ending in a tert-butyl carbamate. No defined stereocenters expected in the linker core; ring conformations typical of THP (chair) dominate but are not configurationally fixed.

Note: Exact atom count, formula, and connectivity for this item were not provided; consult the CoA/Spec Sheet for definitive identifiers.

Synthetic Utility

THP-PEG1-Boc provides orthogonal protection and a minimal ethylene glycol spacer for concise synthetic sequences.

• Functional group reactivity (general)

  • THP-protected alcohol: Stable to many bases and nucleophiles; cleaved under mild acid catalysis to reveal a hydroxyl suitable for further derivatization (e.g., carbonates, esters, Mitsunobu, or activation as sulfonates).
  • Boc-protected amine: Stable to many nucleophiles and mild bases; removed rapidly with TFA or HCl to furnish a primary/secondary amine for amide coupling, urea/carbamate formation, or alkylation.

• Strategic roles

  • Spacer insertion: PEG1 reduces steric congestion and can diminish aggregation in solid-phase or solution-phase couplings.
  • Protecting-group orthogonality: While both are acid-labile, rates and media dependence differ—allowing selective deprotection with careful choice of acid strength, solvent, temperature, and time.

• Typical downstream transformations (literature)

  • After Boc removal: Amide couplings with HATU/EDC/DIC in DMF/DCM; reductive amination in MeCN/EtOH.
  • After THP removal: Esterifications (DCC/DMAP), carbonate formation (p-nitrophenyl chloroformate), or conversion to sulfonates (MsCl/TsCl) followed by nucleophilic substitution.

• Practical tips

  • Minimize adventitious acid during storage/handling to prevent premature deprotection.
  • Use inline drying (molecular sieves) and an inert atmosphere for sensitive steps.
  • Monitor orthogonality empirically; small DoE around acid concentration and solvent polarity helps achieve selective unmasking.

Target Specificity

Not applicable. This product is a small-molecule linker/protecting-group reagent and does not possess biological target specificity such as an antibody, enzyme inhibitor profile, or receptor selectivity. No item-specific target data are provided.