Piv-Leu-OH

Cat. No.: P488172

Synonyms

N-α-Pivaloyl-L-leucine, N-Pivaloyl-Leucine, (2S)-2-(2,2-dimethylpropanamido)-4-methylpentanoic acid

Storage

Room temperature

Specifications

Sinonimi

N-α-Pivaloyl-L-leucine, N-Pivaloyl-Leucine, (2S)-2-(2,2-dimethylpropanamido)-4-methylpentanoic acid

Condizioni di conservazione di stoccaggio

Room temperature

Application Protocols

No assay or immunoassay protocols are specified for this small‑molecule reagent.

• Item-specific tested applications, recommended dilutions, positive controls: Not applicable/not specified for this item.

• Practical usage notes (literature/general)

  • For solution preparation, dissolve in dry DMF or DMSO to make concentrated stocks (e.g., 0.1–0.5 M), filter (0.2 µm PTFE), and use under inert atmosphere for moisture‑sensitive couplings.
  • For weighing/handling, allow bottle to equilibrate to room temperature in a desiccator to avoid moisture condensation before opening.

Biological Roles

• Item-specific biological information: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general context (not a medical claim)

  • Leucine is an essential branched‑chain amino acid central to protein biosynthesis and metabolic regulation; however, in Piv‑Leu‑OH the α‑amino group is acylated, substantially altering biological recognition and transport relative to free L‑leucine.
  • N‑acyl amino acids occur naturally in some metabolic pathways and signaling lipids, but the pivaloyl group is synthetic and increases hydrophobicity and amide stability, generally reducing enzymatic turnover compared to native peptides/amino acids.
  • In biochemical method development, N‑acyl amino acids like Piv‑Leu‑OH can serve as model substrates for studying amidase/esterase selectivity, membrane transport surrogates, or binding in hydrophobic pockets due to the tert‑butyl moiety.

Buffer Applications

Piv‑Leu‑OH is not a dedicated buffering agent. Its single carboxylic acid provides limited buffering capacity near its pKa and is not typically used to prepare laboratory buffers.

• Practical note
  • For aqueous work, it may be dissolved by forming a carboxylate salt at basic pH (>9), but dedicated buffers (e.g., phosphate, Tris, HEPES) should be used to control pH.
  • If incorporated into formulations, verify pH stability of the N‑acyl amide under the intended conditions.

Green Alternatives

• Solvent and reagent choices (literature/general)

  • Prefer greener peptide solvents where feasible: 2‑MeTHF or CPME for extractions and some couplings; EtOAc as a crystallization medium. Replace dichloromethane with EtOAc or Me‑t‑Bu ether when compatible.
  • Coupling reagent selection: Oxyma/EDC or DIC/Oxyma systems avoid HOBt/HOAt energy‑sensitive additives. Consider T3P (propylphosphonic anhydride) in EtOAc/2‑MeTHF as a lower‑hazard alternative to carbodiimides.
  • Base: DIPEA or N‑methylmorpholine in place of tertiary amines with higher vapor pressures.

• Comparative summary (literature/general; tradeoffs)

  • 2‑MeTHF vs DMF: 2‑MeTHF is bio‑derived, lower toxicity, and easier to recover; however, Piv‑Leu‑OH solubility is typically much higher in DMF/DMSO, so concentrations may be limited in 2‑MeTHF.
  • T3P vs DCC: T3P generates water‑soluble byproducts simplifying workup; DCC forms dicyclohexylurea (DCU) waste and can cause allergenicity.
  • EtOAc vs DCM: EtOAc is less problematic environmentally but may require temperature control to match DCM reaction rates/selectivity.

• Process suggestions

  • Evaluate solvent blends (e.g., MeCN/DMF or EtOAc/MeCN) to balance solubility and greener profiles.
  • Implement solvent recovery and in‑process controls to minimize over‑activation that leads to racemization/waste.

Pharmaceutical Uses

No therapeutic or clinical uses are claimed. For research use only (per Product Data).

• Literature/general formulation context (not item‑specific, not a medical claim)
  • N‑acyl amino acids may be explored in medicinal chemistry as pro‑moieties or permeability modifiers; Piv‑Leu‑OH could serve as an intermediate toward esters or amides for structure–property studies.
  • Not typically used as a pharmacopeial excipient. Any use in regulated products would require full qualification and compliance data beyond the scope of this listing.

Physical Properties

• Item-specific properties

  • Appearance: 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.

• Literature/general values (for context; not item specifications)

  • Physical state: typically a crystalline solid for N‑acyl amino acids of this type.
  • Acid–base: contains a carboxylic acid (pKa ~2–3, literature, for α‑amino acid carboxyls when the amine is acylated), amide nitrogen essentially non‑basic.
  • Solubility profile: sparingly soluble in water at neutral pH; increased solubility in basic aqueous media as the carboxylate salt; soluble in polar aprotic organics (DMF, DMSO, NMP) and in alcohols (MeOH, EtOH); limited solubility in nonpolar solvents (hexanes, toluene). (Literature/general)
  • LogP/logD: N‑acylation increases hydrophobicity vs leucine; expected moderate lipophilicity (literature/general trend).
  • Melting point, boiling point, density, refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• General guidance for this class of products (literature/general)

  • Typical expectations for peptide/building‑block grade N‑acyl amino acids:
    • High chemical purity (often ≥95%) to ensure efficient couplings and reproducible stereochemical outcomes.
    • Low residual solvents/inorganics; controlled water content to support moisture‑sensitive activations.
    • Identity confirmation by 1H/13C NMR and HRMS; chiral HPLC to confirm L‑configuration and enantiomeric excess; HPLC area % for assay.
  • UV background: N‑acyl amino acids usually have low UV absorbance above 220–230 nm; HPLC‑grade material supports analytical detection in peptide workflows.
  • Stabilizers: Typically none required; any stabilizer or additive would be disclosed on the CoA. For this item: Not specified.

• Documentation and traceability

  • For method development and regulated labs, request CoA with detailed specifications (purity assay method, residual solvents, inorganic content) and lot‑specific chromatograms.

Reaction and Applications

• Typical research/manufacturing uses (literature/general)

  • Building block for amide/ester derivatization: free carboxyl permits formation of esters and secondary amides while maintaining the N‑pivaloyl protecting group.
  • Peptide chemistry studies: model substrate for N‑acyl transfer kinetics, racemization studies, and coupling reagent benchmarking (e.g., DIC/Oxyma, HATU, EDC/HOBt‑free).
  • Chiral auxiliary/chiral pool derivative: L‑stereocenter can induce diastereocontrol in downstream transformations (e.g., auxiliary‑controlled esterification or amidation, kinetic resolutions).
  • Probing steric effects: the bulky pivaloyl (t‑Bu‑CO‑) on nitrogen attenuates neighboring group participation and can modulate hydrogen bonding vs Boc/Fmoc analogs.

• Representative transformations (literature examples; general guidance)

  • Carbodiimide couplings: Piv‑Leu‑OH + RNH2 → Piv‑Leu‑CONHR (DIC or EDC; Oxyma to suppress racemization; base: DIPEA; solvent: DMF or NMP).
  • Esterification: Fischer (MeOH/H+, Dean–Stark) or Steglich (DCC/DMAP, CH2Cl2) to give methyl/benzyl esters; hydrogenolysis applicable for benzyl deprotection if present elsewhere.
  • Mixed anhydrides/acid chlorides: activation via isobutyl chloroformate or oxalyl chloride (cat. DMF) for subsequent nucleophilic acyl substitution at the carboxyl carbon.
  • Hydrolysis/deprotection studies: base‑promoted hydrolysis can cleave the amide under forcing conditions; pivaloyl amides are notably robust relative to Boc carbamates.

• Practical tips

  • Maintain low temperature (0–10°C) during activation to reduce epimerization at the α‑stereocenter.
  • Use OxymaPure or HOAt alternatives to suppress oxazolone formation/racemization during coupling.
  • Assay by chiral HPLC where stereochemical integrity matters.

Reaction Conditions

Literature/general guidance for typical transformations with N‑acyl amino acids like Piv‑Leu‑OH (not item‑specific specifications):

• Amide coupling at the carboxyl terminus

  • Reagents: DIC (1.1–1.5 eq) + Oxyma (1.1–1.5 eq) or EDC·HCl (1.2–1.5 eq) + Oxyma; base DIPEA (2.0–3.0 eq).
  • Solvent: dry DMF or NMP (0.05–0.2 M).
  • Temperature: 0–25°C to minimize racemization; 1–16 h typical.
  • Notes: preactivate at 0°C for 5–10 min; monitor by HPLC; quench with dilute amine or NaHCO3; avoid HOBt/HOAt for safety.

• Esterification

  • Steglich: DCC (1.1 eq), catalytic DMAP (5–10 mol%), ROH (2–5 eq), CH2Cl2 or EtOAc, 0–25°C, 2–18 h; filter DCU.
  • Fischer: ROH (solvent), catalytic H2SO4 or p‑TsOH, reflux with water removal; beware of epimerization under strongly acidic, high‑temperature conditions.

• Acid chloride/mixed anhydride route

  • Oxalyl chloride or SOCl2 (1.5–2.0 eq), cat. DMF, CH2Cl2, 0–25°C, 0.5–2 h → couple with nucleophile and base at −20 to 0°C.

• Hydrolysis/deprotection

  • N‑pivaloyl amide cleavage generally requires forcing conditions (e.g., refluxing aqueous base or prolonged acidic hydrolysis); plan synthesis accordingly.

• Expected outcomes

  • Couplings often provide good to excellent yields (70–95%, literature) with low epimerization when Oxyma and low temperature are employed.

Safety and Handling

• Item-specific hazard information

  • 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.

• General safety guidance (literature/general; not a substitute for SDS)

  • Expected hazards: low volatility organic solid; may cause irritation to skin, eyes, or respiratory tract; avoid dust generation and inhalation.
  • PPE: lab coat, safety glasses/goggles, appropriate chemical‑resistant gloves (e.g., nitrile). Handle in a fume hood when weighing or dissolving.
  • Incompatibilities: strong bases and strong oxidizers; prolonged exposure to strong base can hydrolyze the amide and/or deprotonate the acid; strong oxidants can react with organic substrates.
  • Handling: minimize dust; use clean, dry tools to avoid adventitious moisture that can affect coupling reactions.
  • First aid (overview): rinse eyes/skin with water for ≥15 min if contacted; move to fresh air if inhaled; seek medical attention if symptoms persist. Always consult the SDS for authoritative instructions.
  • Spill/cleanup: avoid dust; collect by sweeping with damp disposable towels or HEPA vacuum; dispose per local regulations.
  • Fire: treat as combustible organic; use CO2, dry chemical, or foam; firefighters should wear SCBA.

Solvent Selection

Piv‑Leu‑OH behaves as an amphiprotic organic acid with limited aqueous solubility at neutral pH and good solubility in polar aprotic media.

• Practical solvent choices (literature/general)

  • Polar aprotic: DMF, DMSO, NMP — preferred for stock solutions (50–200 mg/mL) and for carbodiimide/uronium coupling reactions.
  • Alcohols: MeOH, EtOH, i‑PrOH — moderate solubility; useful for esterifications or recrystallizations.
  • Water: low solubility at neutral pH; forms soluble carboxylate salts in basic buffers (e.g., pH > 9).
  • Esters/ketones: EtOAc, MeCN — variable solubility; may work for extractions or crystallizations.
  • Nonpolar: hexanes, toluene — generally poor solubility.

• Selection guidance

  • For peptide‑style couplings: dry DMF or NMP to minimize hydrolysis of activated esters; keep water <0.1% when possible.
  • For purification: EtOAc/hexanes or EtOAc/MeOH systems often give good control of polarity; addition of a trace acid (e.g., 0.1% AcOH) can prevent tailing on silica.
  • For salt formation: dissolve in minimal MeOH or MeCN and add organic base (e.g., TEA) to generate the triethylammonium carboxylate, enhancing solubility in organic media.

• Comparative notes (literature/general)

  • DMF vs DMSO: DMF favors easier solvent removal and is more common in peptide coupling; DMSO affords higher solubility but is harder to evaporate.
  • MeCN as greener alternative to DMF is possible for some activations when combined with phase‑transfer or in situ base, but solubility may limit concentration.

Storage and Reconstitution

• Item-specific storage

  • Storage Conditions: Room temperature (per Product Data).
  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

• General guidance (literature/practice)

  • Keep tightly closed in a dry environment; use desiccant if frequent access is expected. Protect from prolonged exposure to light and heat.
  • If long‑term storage is planned, consider 2–8°C in desiccation to minimize gradual hydrolysis; allow to warm in a desiccator before opening to avoid moisture uptake.
  • Reconstitution: dissolve in dry DMF, DMSO, or MeOH to prepare stock solutions. For aqueous applications, adjust pH with base to form the carboxylate for improved solubility. Filter through 0.2 µm PTFE prior to use in moisture‑sensitive reactions.
  • Freeze‑thaw: for solution stocks, aliquot to avoid repeated freeze–thaw cycles; store organic solutions at ≤−20°C in moisture‑tight vials when compatible.

• Stability notes

  • N‑pivaloyl amide is relatively robust; the free acid can slowly esterify or hydrolyze under inappropriate conditions. Always verify integrity by HPLC/NMR before critical uses.

Structure and Identity

Brief description: Piv‑Leu‑OH is the N‑pivaloylated derivative of L‑leucine bearing a free carboxylic acid. It is an N‑acyl amino acid building block useful in peptide and amide chemistry.

• Item-specific (from Product Data)

  • SKU: P488172
  • Product Name: Piv-Leu-OH
  • Storage Conditions: Room temperature
  • Other identifiers (CAS, CID, InChIKey, SMILES, Molecular Formula, Molecular Weight): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identity (for context; not item specifications)

  • Common chemical description: N‑pivaloyl‑L‑leucine (N‑(tert‑butanoyl)‑L‑leucine)
  • Expected core functional groups: secondary amide (pivaloyl amide), carboxylic acid, aliphatic isobutyl side chain, single stereocenter (L configuration)
  • Representative SMILES (literature): CC(C)CC@@HC(=O)O
  • Approximate molecular formula (literature): C11H21NO3
  • Approximate molecular weight (literature): ~215.29 g/mol

• 2D structural description (literature):

  • Backbone: an α‑amino acid framework with the amino nitrogen acylated by a tert‑butanoyl (pivaloyl, t‑Bu–CO–) group, retaining the α‑carboxylic acid.
  • Side chain: sec‑butyl/isobutyl group of leucine (–CH2–CH(CH3)2).
  • Stereochemistry: one chiral center at the α‑carbon; the L (S) configuration in the literature form.

Synthetic Utility

• Functional group portfolio (literature/general)

  • Reactive carboxylic acid enables formation of esters, amides, anhydrides, and activated esters (e.g., NHS, pNP esters).
  • N‑pivaloyl secondary amide is robust and can modulate conformation and H‑bonding relative to free amines or Boc/Fmoc carbamates.
  • Single stereocenter (L) provides chiral induction potential.

• Use cases

  • As a chiral acyl component: introduce the Piv‑Leu‑ fragment into target molecules, then manipulate the carboxyl terminus.
  • As a protecting/steric element: the pivaloyl group provides significant steric hindrance, reducing side reactions at nitrogen and adjacent centers during downstream chemistry.
  • Intermediate to heterobifunctional linkers: convert the acid to an activated ester while retaining a masked amine (as an amide) to control sequential reactivity.

• Retrosynthetic logic

  • Target amide/ester → activate Piv‑Leu‑OH (e.g., DIC/Oxyma, T3P) → couple to nucleophile under mild conditions while monitoring for epimerization.
  • If free amine functionality is ultimately required, consider introducing Piv late or select alternative N‑protecting groups (e.g., Boc) due to the difficulty of N‑deacylating pivaloyl amides.

Target Specificity

This product is a small‑molecule building block, not an antibody or biological affinity reagent.

• Item-specific data (antigen, clone, isotype, species reactivity): Not applicable/not specified for this item.