VH032-CH2-Boc , CAS No.2827750-24-1

CAS: 2827750-24-1 Cat. No.: V1449882 Formula: C₃₀H₄₂N₄O₆S Molecular Weight: 586.74

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

VH032 -CH2-Boc is a Boc-modified VH032 that serves as a ligand for VHL and recruits von Hippel-Lindau (VHL) proteins. VH032 -CH2-Boc will remove the protecting group under acidic conditions and be directly used in PROTAC molecule synthesis. VH032 -CH2-Boc is a key intermediate in the synthesis of PROTAC based on VHL ligand.

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

586.74

Application Protocols

No tested biological application protocols (e.g., WB, IHC, IF, FC) or recommended dilutions are provided for this small-molecule building block.

General laboratory protocol examples (for synthesis context only; not item specifications):

• Boc deprotection (example): Dissolve the substrate in DCM (0.05–0.1 M). Add TFA to 50–100% v/v TFA. Stir at 0–25°C for 45–90 min. Remove volatiles under reduced pressure, co-evaporate with toluene, and proceed to coupling without prolonged storage of the TFA salt.
• Amide coupling (example): To a solution of the amine (1.0 equiv) and carboxylic acid partner (1.1 equiv) in DMF (0.05–0.2 M), add HATU (1.1 equiv) and DIPEA (2–3 equiv) at 0–25°C. Stir 2–6 h, monitor by LC–MS, quench with water, extract, and purify by flash or prep-RP-HPLC.

All protocols should be optimized for the specific linker/warhead pair and verified on small scale prior to scale-up.

For any application-specific directions supplied with your lot, defer to the CoA/Spec Sheet.

Biological Roles

General/literature context for VH032-derived ligands:

• E3 ligase recruitment: VH032 is a well-characterized ligand for the von Hippel–Lindau (VHL) E3 ubiquitin ligase complex. When incorporated into bifunctional molecules, it enables proximity-induced ubiquitination of target proteins (literature). VH032-CH2-Boc derivatives serve as synthetic precursors to such constructs.
• Stereochemical sensitivity: Binding to VHL is stereoselective, relying on hydroxyproline-based topology and hydrogen-bond networks in the VHL pocket. Maintaining correct absolute configuration is essential for affinity (literature).
• Not a biological buffer, nutrient, or metabolic intermediate: The compound is a synthetic building block; it does not have intrinsic metabolic or signaling roles outside designed chemical biology probes.

Important notes specific to this catalog item:

• No biological activity data, binding constants, or cellular performance metrics are provided in the Product Data. Users should not infer potency or efficacy from the name alone; verify structure and evaluate activity after conjugation in your specific system.
• For research use only: Not intended for use in humans or animals. Experimental use should follow institutional biosafety policies and appropriate containment when testing downstream conjugates in cells.

Buffer Applications

This product is not a buffering reagent and is not typically used to prepare pH buffer systems.

Practical guidance:

• If using in biochemical assays, dissolve the compound (or its conjugates) first in an appropriate organic co-solvent (e.g., DMSO) before dilution into assay buffers (e.g., HEPES, PBS). Maintain final organic cosolvent at low percentages (typically ≤1–2% v/v) to preserve protein integrity.
• For conjugates bearing ionizable groups, choose buffers that do not compete with binding equilibria or interfere with E3 ligase or target engagement (e.g., avoid high primary amine concentrations when measuring amide-forming steps in situ).

Item-specific buffer properties (pKa, buffer range) are not applicable.

Green Alternatives

Greener choices relate mainly to solvent and coupling-reagent selection during use of this building block.

• Solvents:
  • Replace DCM with EtOAc or 2-MeTHF for extractions and some couplings when feasible; for Boc deprotection, explore TFA in EtOAc or anisole co-solvent systems, though DCM remains common.
  • Use 2-MeTHF in place of THF to reduce peroxide concerns and improve sustainability (biorenewable feedstock), noting occasional solubility differences.
  • Prefer Me-THF/EtOAc over acetonitrile when reaction compatibility allows.
• Coupling reagents:
  • Explore greener carbodiimides (EDC·HCl, water-compatible) and OxymaPure instead of HOBt/HOAt (safety advantages). For amide couplings, DMTMM can be an efficient, less hazardous option in some contexts.
• Workup and purification:
  • Minimize halogenated waste by using heptane/EtOAc gradients or EtOAc/IPA systems in flash chromatography.
  • Recrystallization or trituration can sometimes replace extensive column chromatography for Boc-protected intermediates.

Comparison (general):

• DCM vs EtOAc: EtOAc is greener (biodegradable, lower toxicity) but may provide lower solubility for highly polar substrates; DCM offers excellent volatility and solvation for TFA but is more hazardous.
• THF vs 2-MeTHF: 2-MeTHF has better safety/green profile and water tolerance; may change reaction rates and selectivity.

Always verify yield/selectivity impacts when substituting greener systems; run small pilots before scale-up.

Pharmaceutical Uses

• This product is offered for research use only. It is not an approved pharmaceutical ingredient, excipient, or drug substance.
• No pharmacopeial monograph or excipient status is provided in the Product Data.

Context (general):

• VH032-derivative building blocks are commonly used in discovery research to prepare heterobifunctional degraders and related chemical biology probes. Any consideration of formulation or dosage is outside the scope of this research chemical.
• If later-stage developability studies are envisaged for conjugates prepared from this intermediate, preformulation assessment (solubility, stability, hygroscopicity, polymorphism) should be conducted on the final construct rather than on this protected precursor.

Conclusion: No pharmaceutical-use claims apply. For regulated applications, source chain-of-custody documentation and quality attributes from the CoA/Spec Sheet of the final research compound.

Physical Properties

Item-specific properties (from Product Data):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not applicable/typically not reported for multifunctional solids; Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not applicable for solids; Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for VH032-CH2-Boc-type solids (informational only, not item specifications):

• Physical state: Usually a white to off-white solid.
• Solubility profile: Often soluble in polar aprotic organic solvents (e.g., DMSO, DMF, NMP, acetonitrile) and moderately soluble in chlorinated or ethereal solvents (e.g., DCM, THF). Aqueous solubility is typically low unless salts are formed.
• Ionization/functional groups: Presence of carbamate (Boc), amide(s), and hydroxyl groups; Boc suppresses basicity of the amine until deprotection.

Notes for handling (general):

• Hygroscopicity is generally low to moderate for Boc-protected VHL-ligand derivatives, but moisture uptake can affect weighing accuracy; handle rapidly in dry air or under inert gas when precision is critical.
• For accurate solubility and thermal metrics relevant to your lot, consult the CoA/Spec Sheet and perform a quick preformulation solubility screen in intended solvents.

Quality & Grades

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

Interpretation and practical notes:

• In absence of a declared grade (e.g., “>98%,” “HPLC grade,” or “Biotech grade”), users should verify assay purity, residual solvent profile, and identity (NMR, LC–MS, HPLC) on the lot-specific CoA. This is especially important for elaborated ligands used in structure–activity studies where minor impurities can propagate into final conjugates.
• UV background: If using in analytical HPLC method development, note that VH032-type chromophores often absorb in the low-UV range due to amide/carbonyl content; assess purity with orthogonal detectors (UV + MS, or ELSD) when possible.
• Stabilizers: None are indicated in the Product Data. If present in a given lot (e.g., trace acid to prevent Boc migration/deprotection), this will appear on the CoA/Spec Sheet.
• Documentation: For regulated or high-rigor studies, request and archive CoA, synthesis origin, and any available impurities profile. If elemental specs, water content, or residual palladium/nickel are critical to your application, these must be confirmed analytically as they are Not specified for this item; refer to CoA/Spec Sheet.

Recommendation: Perform a quick incoming QC (1H NMR, LC–MS, HPLC purity) before committing to multi-gram conjugation or library synthesis.

Reaction & Applications

Manufacturer-stated application: For research use only. No specific application text provided in Product Data.

General/literature context for VH032-CH2-Boc-type reagents:

• PROTAC/Degrader precursor: The VH032 core binds the VHL E3 ubiquitin ligase (literature). The –CH2–NH–Boc terminus serves as a protected primary amine handle enabling installation of linkers or warheads after Boc removal.
• Conjugation strategies:
  • Amide formation: After Boc deprotection (e.g., TFA/DCM), couple the liberated amine to carboxylic-acid functionalized linkers/warheads using HATU/HOAt/DIPEA, EDCI/HOBt/DIPEA, or acid chlorides/anhydrides.
  • Urea/carbamate linkages: React the deprotected amine with isocyanates/chloroformates or via CDI-activated carbonates to fine-tune polarity and stability.
  • Reductive amination: If the counterpart bears an aldehyde/ketone, the free amine can be coupled under NaBH3CN or BH3CN analogs in MeOH/THF with AcOH buffering.
• Solid-phase/parallel synthesis: Boc protection is compatible with solid-phase strategies where acid-labile steps are acceptable; orthogonal protection on other sites enables rapid library generation.
• SAR exploration: Varying linker length, branching, and polarity from the –CH2–NH position modulates ternary complex formation and degradation efficiency (literature). The –CH2– spacer imparts flexibility while maintaining the VHL-binding pharmacophore.

Practical tips:

• Keep Boc intact during early-stage manipulations to minimize side reactions; schedule TFA deprotection immediately prior to coupling.
• Use mild bases (DIPEA, TEA) and avoid strong nucleophiles that could transcarbamylate or open sensitive motifs.

Reaction Conditions

The following are general literature/practice guidelines for VH032-CH2-Boc-type intermediates; they are not specifications for this item.

• Boc deprotection:
  • Reagents: TFA in DCM (50–100% TFA v/v), or TFA neat for short exposures.
  • Conditions: 0–25°C, 0.5–2 h. Protect moisture-sensitive partners. Typical workup via co-evaporation with toluene, then basify and extract if necessary.
  • Notes: Scavengers (anisole, triethylsilane) can suppress carbocation-mediated side reactions where sensitive aromatics are present.
• Amide coupling (post-deprotection):
  • Reagents: HATU/DIPEA or EDCI/Oxyma/DIPEA in DMF, NMP, or DCM.
  • Conditions: 0–25°C, 1–16 h; dilute to manage urea precipitation (EDCI). Monitor by LC–MS.
  • Notes: Minimize excess coupling reagent to reduce guanidinium/urea byproducts.
• Urea/carbamate formation:
  • Reagents: CDI (then add alcohol or amine partner), triphosgene (carefully), or chloroformates/isocyanates.
  • Conditions: 0–25°C; inert atmosphere; 2–6 h typical.
• Reductive amination:
  • Reagents: NaBH3CN or picoline-borane; solvent MeOH/THF/DMF blends; AcOH or HOAc/TEA buffer.
  • Conditions: 0–25°C, 2–12 h; control pH ~5–6 for selectivity.

Purification:

• Flash chromatography with EtOAc/hexanes → MeOH/DCM gradients; for polar products, prep-HPLC (RP, 0.1% TFA or formic acid modifiers) is often preferable.

Yields:

• Reported step yields for analogous couplings often range 50–90% depending on linker and warhead (literature). Optimize stoichiometry, base, and solvent to improve conversions.

Safety & Handling

Authoritative safety data must be obtained from the product SDS.

Item-specific hazard data from Product Data:

• GHS classification: Not specified for this item; refer to SDS.
• Signal word: Not specified for this item; refer to SDS.
• H-statements: Not specified for this item; refer to SDS.
• Pictograms: Not specified for this item; refer to SDS.

General lab-safety guidance for Boc-protected, multifunctional organic solids (informational only):

• PPE: Wear lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of dust or solvent vapors during dissolution.
• Avoid: Inhalation of dust, contact with skin/eyes, and ingestion. Wash thoroughly after handling.
• Incompatibilities: Strong acids will remove the Boc group; strong bases and potent nucleophiles can trigger undesired side reactions in sensitive moieties. Oxidizers may react with organic materials—store separately.
• First aid (overview, not a substitute for SDS):
  • Inhalation: Move to fresh air; seek medical attention 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 continues.
  • Ingestion: Rinse mouth; do not induce vomiting; obtain medical advice.
• Waste: Collect organic-solvent rinses and solid residues in suitable halogenated/non-halogenated waste streams per local regulations.

Always consult and follow the product’s SDS and your institutional EHS policies.

Solvent Selection

Given this product is a multifunctional organic solid used as a coupling handle, solvent choice is typically driven by reaction chemistry rather than by the compound acting as the solvent.

General guidance (literature/practice):

• Polar aprotic solvents (e.g., DMF, N,N-dimethylacetamide, NMP, DMSO) are commonly preferred for amide couplings and urea/carbamate formations from Boc-protected precursors.
• Chlorinated solvents (e.g., DCM) are often used for Boc deprotection (TFA/DCM mixtures) and for acid chloride or HATU-mediated couplings when solubility permits.
• Ethers/esters (THF, 2-MeTHF, EtOAc) can be useful for extractions and for less polar coupling systems; THF/MeOH blends may aid in crystallization or trituration of Boc-protected intermediates.
• Alcohols are typically avoided during Boc installation/retention steps in strong acid, but may be used in workups.

Selection tips:

• Start with DMF or DCM depending on reagent system; if solubility is limiting, add 5–20% DMSO or switch to NMP.
• For moisture-sensitive couplings, ensure anhydrous solvent and inert atmosphere. Pre-dry DMF (molecular sieves) if low water is essential.
• For purification, MeOH/DCM or EtOAc/hexanes gradients often separate Boc-protected species from deprotected/byproduct materials; monitor by TLC and LC–MS.

Note: Solubility and crystallization behavior are substrate- and lot-dependent; confirm on small scale prior to scale-up.

Storage & Reconstitution

Item-specific storage and shipping (from Product Data):

• Storage conditions: Store at -20°C.
• Shipped in: Ice chest + ice pads.

General handling recommendations:

• Keep tightly closed in original container with desiccant. Allow the vial to warm to room temperature in a desiccator before opening to minimize condensation.
• Protect from prolonged exposure to acids or bases that could remove Boc or promote side reactions. Avoid repeated freeze–thaw of DMSO stock solutions; aliquot if solution storage is needed.

Reconstitution (general guidance for small-molecule solids; not a specification):

• Prepare concentrated stocks in anhydrous DMSO or DMF (e.g., 10–50 mM) for synthetic operations; verify solubility empirically. For immediate use in couplings, dissolve directly in anhydrous DMF/DCM as required by the reagent system.
• If aqueous use is required for analytical purposes, first dissolve in DMSO, then dilute with buffer to the lowest feasible final DMSO fraction consistent with solubility.

Stability notes:

• Boc-protected analogs are generally stable under dry, neutral conditions at -20°C. Avoid exposure to strong acids (Boc cleavage) and strong bases or nucleophiles that may cause degradation.

For definitive stability, impurity, and solution-holding-time information, consult the lot-specific CoA/Spec Sheet.

Structure & Identity

• Item: VH032-CH2-Boc (SKU: V1449882)
• CAS: 2827750-24-1
• 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 overview (general/literature context):

• VH032-CH2-Boc designations in the literature typically describe a derivative of the VHL E3 ligase ligand “VH032” bearing a methylene (–CH2–) spacer terminating in a Boc-protected amine (–CH2–NH–Boc). This motif functions as a handle for linker elaboration in heterobifunctional molecules (e.g., PROTACs), enabling coupling through deprotection to reveal a primary amine.
• Key functional features (general):
  • A VHL-binding hydroxyproline-based core (as in VH032 ligands, literature) that confers E3 ligase recruitment capability.
  • A pendant –CH2–NHBoc group that masks nucleophilicity, enhancing stability and handling during multistep synthesis; Boc is removable under mild acid.
• Stereochemistry (general): VH032-type ligands incorporate a defined stereochemistry at the hydroxyproline center(s) critical for VHL engagement (literature). The specific stereochemical descriptors for this catalog item are not specified here; consult the CoA/Spec Sheet.

Note: Because structure identifiers (SMILES/InChI) are not provided in the Product Data, users should confirm exact structure and stereochemistry from the item’s CoA/Spec Sheet prior to route design.

Synthetic Utility

VH032-CH2-Boc-type intermediates are versatile E3-ligase-ligand handles tailored for modular synthesis of bifunctional molecules.

Key functional elements (general):

• Boc-protected primary amine: Acid-labile, enabling late-stage unveiling of a nucleophile for coupling. Compatible with mild bases and many peptide-coupling reagents; tolerates a broad set of functional groups during upstream steps.
• VH032 core: Provides the VHL-binding pharmacophore; typically contains multiple amide and hydroxyl groups that influence solubility and polarity of conjugates.
• –CH2– spacer: Offers conformational flexibility and spacing between the VHL-ligand core and downstream linker or warhead, aiding ternary complex formation tuning.

Representative transformations (literature/practice):

• Boc deprotection: TFA/DCM (1:1 to 1:4) at 0–25°C, 0.5–2 h, then co-evaporation with toluene to remove TFA. Neutralize and proceed without isolation where possible.
• Amide coupling: HATU or EDCI/Oxyma with DIPEA in DMF/DCM, 0–25°C, 1–16 h. Monitor by LC–MS; quench and purify by flash or prep-HPLC.
• Urea/carbamate formation: Triphosgene or CDI/chloroformate routes to vary linker polarity; perform at 0–25°C with base (DIPEA).
• Reductive amination: For aldehyde-bearing linkers, use NaBH3CN or picoline-borane in MeOH/THF with AcOH buffer.

Utility in retrosynthesis: Serves as a convergent fragment; assemble the VHL half independently, then couple to a diversified linker/warhead arm to accelerate SAR.

Target Specificity

Item-specific biological target data are not provided in the Product Data for SKU V1449882.

General/literature context:

• VH032-derived ligands are designed to engage the VHL E3 ubiquitin ligase complex. However, specificity, affinity (Kd), and ternary-complex behavior depend strongly on the exact structure, stereochemistry, and the appended linker/warhead.

For this product:

• Target, clone, isotype, or species reactivity fields are not applicable (this is a small-molecule building block, not an antibody or protein reagent).
• Do not assume target potency or selectivity. Confirm identity via CoA/Spec Sheet, then characterize any final conjugate in the intended biochemical/cellular assays.