(R)-2-(Boc-amino)-4-methyl-4-pentenoic Acid — Chiral Amino Acid Building Block (≥98% HPLC / ≥99% cGMP)
(R)-2-(Boc-amino)-4-methyl-4-pentenoic acid (CAS 103986-33-0, C₁₁H₁₉NO₄, MW 229.27 g/mol) — a Boc-protected chiral amino acid with a terminal alkene side chain for peptide stapling, ring-closing metathesis (RCM), click chemistry, and PROTAC linker chemistry. This Boc-D-allylglycine derivative is a versatile pharmaceutical intermediate: the Boc (tert-butoxycarbonyl) protecting group enables selective Fmoc-SPPS incorporation, while the terminal alkene serves as a chemical handle for hydrocarbon stapling, thiol-ene click reactions, and olefin cross-coupling. Available in ≥98% HPLC (Research/Pharma Intermediate Grade) and ≥99% HPLC (cGMP available) with ≥99% enantiomeric excess. ISO 9001:2015, ISO 22000, FDA, HALAL, KOSHER certified. Bulk manufacturer and wholesale supplier — premium chiral amino acid building blocks from UPOR Biotech.
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(R)-2-(Boc-amino)-4-methyl-4-pentenoic acid (synonyms: (R)-2-((tert-Butoxycarbonyl)amino)-4-methyl-4-pentenoic acid; Boc-D-allylglycine derivative; Boc-(R)-2-amino-4-methyl-4-pentenoic acid, CAS 103986-33-0, C₁₁H₁₉NO₄, MW 229.27 g/mol) is a chiral, Boc-protected non-proteinogenic amino acid bearing a terminal alkene in its side chain — a privileged building block in modern peptide and bioconjugation chemistry. The compound combines three critical functional elements in a single, well-defined chiral scaffold: (1) a Boc (tert-butoxycarbonyl) protected alpha-amine that remains stable under Fmoc-SPPS deprotection conditions (20% piperidine/DMF) and is orthogonally cleaved with TFA — enabling site-selective peptide chain elongation; (2) a terminal alkene (4-methyl-4-pentenoic acid) side chain that serves as a versatile chemical handle for ring-closing metathesis (RCM) with Grubbs or Hoveyda-Grubbs catalysts, thiol-ene click chemistry, and transition-metal-catalyzed cross-coupling (Heck, Suzuki-Miyaura); and (3) a defined (R)-stereochemistry at the alpha-carbon, providing the correct spatial orientation for alpha-helical peptide architectures in stapled peptide design. The terminal alkene distinguishes this building block from standard Boc-amino acids — it introduces a covalent anchor point for hydrocarbon stapling (i, i+4 or i, i+7 cross-links), PROTAC linker attachment, and bioconjugation to targeting ligands or fluorophores.
This compound is an essential intermediate in three rapidly growing pharmaceutical modalities. Stapled peptide therapeutics use RCM to cross-link two alkene-bearing residues, locking the peptide into a bioactive alpha-helical conformation with dramatically improved proteolytic stability (up to 30-fold increase in serum half-life), cell permeability (enhanced by the hydrophobic hydrocarbon staple), and target binding affinity (reduced entropic penalty of binding). PROTAC (PROteolysis TArgeting Chimera) linker chemistry exploits the terminal alkene as a conjugation site for attaching E3 ligase-recruiting moieties via olefin cross-coupling or thiol-ene click chemistry. Peptide-drug conjugates and bioconjugates utilize the alkene for site-specific attachment of cytotoxic payloads, fluorescent probes, or PEG chains. UPOR Biotech supplies this chiral amino acid in two grades: ≥98% HPLC (Research/Pharma Intermediate Grade) with ≥99% ee for discovery and lead optimization, and ≥99% HPLC (cGMP) with ≥99.5% ee for IND-enabling studies, clinical trial material manufacturing, and commercial production. OEM and private label custom synthesis and derivatization services available.
Boc vs Fmoc Orthogonal Protection — Why the Boc Group Enables Selective Fmoc-SPPS Incorporation of Alkene-Functionalized Amino Acids
The choice of N-alpha protecting group is critical for successful solid-phase peptide synthesis with alkene-bearing amino acids. Boc protection (used in this product) is the preferred strategy when the target peptide requires Fmoc-SPPS assembly: the Boc group is completely stable under the basic Fmoc-deprotection conditions (20% piperidine/DMF, 2 × 5 min) and the mildly acidic coupling conditions (HBTU/DIPEA or DIC/HOBt), ensuring that the alpha-amine remains protected and unavailable for undesired chain extension at that site. The Boc group is then selectively removed with TFA (20–50% in DCM) after the full peptide sequence has been assembled on-resin — this orthogonal deprotection strategy enables precise, site-specific incorporation of the alkene-bearing residue at any desired position within the peptide chain. In contrast, an Fmoc-protected alkene amino acid would lose its N-alpha protection during every piperidine cycle, leading to uncontrolled chain branching. The terminal alkene — the unique differentiator of this building block — is chemically orthogonal to both Boc and Fmoc chemistry: it is stable to piperidine (Fmoc removal), TFA (Boc removal and resin cleavage), and all standard coupling reagents. This three-way orthogonality (Boc, Fmoc, alkene) allows chemists to independently control: (1) peptide chain elongation via Fmoc-SPPS cycles, (2) N-terminal deprotection via TFA treatment, and (3) olefin cross-linking or conjugation via Grubbs-catalyzed RCM, thiol-ene, or metal-catalyzed cross-coupling — all without protecting group interference. For stapled peptide synthesis, this compound is typically incorporated at the i position paired with another alkene amino acid at i+4 or i+7, enabling on-resin RCM macrocyclization immediately after chain assembly and N-terminal Boc removal.
Technical Specifications
| Property | Specification |
|---|---|
| Product Name | (R)-2-(Boc-amino)-4-methyl-4-pentenoic Acid |
| Synonyms | (R)-2-((tert-Butoxycarbonyl)amino)-4-methyl-4-pentenoic acid; Boc-D-allylglycine derivative; Boc-(R)-2-amino-4-methyl-4-pentenoic acid; (R)-N-Boc-2-amino-4-methyl-4-pentenoic acid |
| CAS Number | 103986-33-0 |
| Molecular Formula | C₁₁H₁₉NO₄ |
| Molecular Weight | 229.27 g/mol |
| Product Type | Chiral amino acid building block — pharmaceutical intermediate for peptide synthesis, stapled peptides, and bioconjugation |
| Key Advantage | Boc-protected chiral amino acid with terminal alkene — enables orthogonal Fmoc-SPPS incorporation with downstream RCM, click chemistry, and olefin cross-coupling for peptide stapling and PROTAC linker attachment |
| Appearance | White to off-white crystalline powder |
| Assay (Research / Pharma Intermediate Grade) | ≥98.0% (HPLC, area normalization) |
| Assay (cGMP Grade) | ≥99.0% (HPLC, area normalization) |
| Enantiomeric Excess (ee) | ≥99.0% (Research Grade); ≥99.5% (cGMP Grade) — determined by chiral HPLC |
| Identification | ¹H NMR (400 MHz) and ¹³C NMR (100 MHz) conforms to reference standard; ESI-MS or HRMS molecular ion [M+H]⁺ and [M+Na]⁺ consistent with C₁₁H₁₉NO₄; IR spectrum conforms to structure |
| Loss on Drying | ≤1.0% (60°C, vacuum, 4 hours) |
| Residue on Ignition | ≤0.1% |
| Melting Point | Reported range 68–72 °C (varies with crystallinity; lot-specific value provided on COA) |
| Specific Optical Rotation | [α]ᵇ²⁰ = +15.0° to +20.0° (c = 1.0, MeOH) — lot-specific value provided on COA |
| Solubility | Soluble in DCM, DMF, DMSO, THF, ethyl acetate, methanol; slightly soluble in water; practically insoluble in hexane |
| Heavy Metals (Total) | ≤10 ppm (as Pb) |
| Elemental Impurities | Pb ≤2 ppm; As ≤1 ppm; Hg ≤1 ppm; Cd ≤1 ppm (USP <232> / ICH Q3D compliant); Ru ≤10 ppm (residual RCM catalyst — tested and reported for cGMP grade) |
| Microbial Limits | TAMC ≤100 CFU/g; TYMC ≤10 CFU/g (USP <61> / EP <2.6.12>); Pathogens (E. coli, Salmonella, S. aureus, P. aeruginosa) — Absent in 1 g (USP <62> / EP <2.6.13>) |
| Residual Solvents | USP <467> / EP <5.4> / ICH Q3C Class 3 compliant; individual residual solvent ≤0.5% (5000 ppm) per ICH Q3C Option 1 limits |
| Chiral Purity (HPLC) | Single enantiomer ≥99.0% (Research Grade); ≥99.5% (cGMP Grade) — opposite enantiomer ≤0.5% by chiral HPLC (Chiralpak or equivalent column) |
| Boc Content (TGA/Titration) | Boc protecting group intact — confirmed by ¹H NMR (tert-butyl singlet at δ ~1.45 ppm, 9H integration) and TGA weight loss profile |
| Grade / Standards | Research / Pharma Intermediate Grade (≥98% HPLC, ≥99% ee); cGMP Grade (≥99% HPLC, ≥99.5% ee, ICH Q7 cGMP manufactured) |
| DMF | Type II Drug Master File support available (cGMP grade); Letter of Authorization upon signed Confidentiality Agreement |
| Certifications | ISO 9001:2015, ISO 22000, HACCP, FDA Facility Registration, HALAL, KOSHER, Non-GMO, BSE/TSE-Free |
| Packaging | 1 g / 5 g / 10 g / 25 g amber glass vials with PTFE-lined cap under argon; 100 g / 500 g / 1 kg HDPE bottles with double PE liner under nitrogen |
| Storage | –20 °C ± 5 °C, tightly sealed in original container under inert gas (argon or nitrogen), protect from moisture and light |
| Shelf Life | 2 years from date of manufacture under recommended storage conditions; retest date applied after 2 years |
Key Benefits — (R)-2-(Boc-amino)-4-methyl-4-pentenoic Acid
Boc-Protected for Orthogonal Fmoc-SPPS — Selective Peptide Incorporation
The Boc protecting group remains completely stable under Fmoc-SPPS conditions (20% piperidine/DMF, coupling reagents), enabling site-specific incorporation of this alkene-bearing amino acid at any desired position. Orthogonal TFA deprotection after chain assembly provides precise control over peptide architecture.
Orthogonal ProtectionTerminal Alkene Handle — RCM, Click Chemistry & Cross-Coupling Ready
The 4-methyl-4-pentenoic acid side chain provides a reactive terminal alkene for ring-closing metathesis (hydrocarbon stapling with Grubbs/Hoveyda-Grubbs catalysts), thiol-ene click chemistry, and palladium-catalyzed cross-coupling — the essential building block for stapled peptide therapeutics and PROTAC linkers.
Terminal AlkeneDual-Grade Supply — Research (≥98%) & cGMP (≥99%) with Full Traceability
Research/Pharma Intermediate Grade (≥98% HPLC, ≥99% ee) for discovery and lead optimization. cGMP Grade (≥99% HPLC, ≥99.5% ee) manufactured under ICH Q7 with Type II DMF support for IND-enabling studies, clinical trial material, and commercial production. Both grades include full COA and analytical data package.
≥98% / cGMPDefined (R)-Stereochemistry — Correct Helical Geometry for Stapled Peptide Design
The (R)-configuration at the alpha-carbon provides the correct spatial orientation for alpha-helical peptide architectures. Combined with high enantiomeric excess (≥99% ee Research / ≥99.5% ee cGMP), this ensures reproducible stapling geometry, target binding affinity, and pharmacokinetic properties in your peptide therapeutics.
Chiral IntegrityApplications
Stapled Peptide Therapeutics
Hydrocarbon-stapled peptides for targeting intracellular protein-protein interactions (PPIs). The terminal alkene enables i, i+4 or i, i+7 on-resin RCM macrocyclization with Grubbs catalysts — producing protease-resistant, cell-permeable alpha-helical peptide drugs for oncology, metabolic disease, and infectious disease targets.
PROTAC Linker Chemistry & Targeted Protein Degradation
Terminal alkene as a conjugation site for attaching E3 ligase ligands (VHL, CRBN, IAP) via olefin cross-coupling or thiol-ene chemistry. Enables modular PROTAC assembly with defined linker geometry for ternary complex formation and efficient ubiquitin-proteasome recruitment.
Ring-Closing Metathesis (RCM) & Macrocyclic Peptide Synthesis
Key substrate for RCM-based peptide macrocyclization using Grubbs 1st/2nd generation or Hoveyda-Grubbs catalysts. The terminal alkene reacts efficiently under mild conditions (DCM or DCE, 25–40 °C, 2–24 h) to form cyclic peptides with improved conformational stability and target selectivity.
Click Chemistry & Bioconjugation
Thiol-ene click chemistry with cysteine-containing peptides, proteins, or targeting ligands for site-specific bioconjugation. Compatible with photoinitiated (UV 365 nm, Irgacure 2959) or thermal (VA-044) radical initiation — enabling clean, bioorthogonal conjugation without metal catalysts.
Fmoc-SPPS Peptide Synthesis — Orthogonal Building Block Strategy
Boc-protected alpha-amine enables selective Fmoc-SPPS incorporation without interference from standard piperidine deprotection cycles. The three-way orthogonality (Boc / Fmoc / alkene) provides complete synthetic control for complex, multifunctional peptide architectures in drug discovery.
Chiral Drug Intermediate — Asymmetric Synthesis of Pharmaceutical APIs
Defined (R)-stereochemistry and high enantiomeric excess make this compound a reliable chiral pool starting material for the asymmetric synthesis of pharmaceutical APIs, peptidomimetic drug candidates, and constrained amino acid derivatives for medicinal chemistry programs.
Frequently Asked Questions
(R)-2-(Boc-amino)-4-methyl-4-pentenoic acid (CAS 103986-33-0, C₁₁H₁₉NO₄, MW 229.27 g/mol) is a chiral, Boc-protected non-proteinogenic amino acid building block with a terminal alkene side chain. The Boc group remains stable under Fmoc-SPPS conditions (20% piperidine/DMF) and is orthogonally removed with TFA — enabling site-specific incorporation at any desired position within a peptide sequence. The terminal alkene then serves as a chemical handle for downstream modifications: ring-closing metathesis (RCM) for hydrocarbon stapling, thiol-ene click chemistry for bioconjugation, and olefin cross-coupling for PROTAC linker attachment. This three-function design (Boc protection, alkene reactivity, defined (R)-stereochemistry) makes it an essential building block for stapled peptide therapeutics, PROTAC degraders, and peptide-drug conjugates. UPOR Biotech provides both Research Grade (≥98% HPLC, ≥99% ee) and cGMP Grade (≥99% HPLC, ≥99.5% ee) with full analytical documentation.
The terminal alkene in the 4-methyl-4-pentenoic acid side chain is the reactive handle that enables ring-closing metathesis (RCM) for hydrocarbon peptide stapling. In a typical workflow: (1) This amino acid is incorporated at position i of the peptide via Fmoc-SPPS (Boc remains intact during chain elongation). (2) A second alkene-bearing amino acid is incorporated at position i+4 or i+7. (3) The N-terminal Boc is removed with TFA. (4) On-resin RCM is performed using a ruthenium-based catalyst (Grubbs I/II or Hoveyda-Grubbs I/II) in DCM or DCE at 25–40 °C for 2–24 hours — the two terminal alkenes undergo metathesis to form an internal olefin hydrocarbon cross-link. (5) The stapled peptide is cleaved from the resin and purified. The resulting hydrocarbon staple locks the peptide into an alpha-helical conformation, providing dramatically improved proteolytic stability (up to 30× serum half-life increase), enhanced cell permeability (the hydrophobic staple facilitates membrane penetration), and increased target binding affinity (pre-organized binding conformation reduces entropic penalty). Beyond RCM, the terminal alkene also enables thiol-ene click chemistry for conjugation to thiol-containing biomolecules, and transition-metal-catalyzed cross-coupling (Heck, Suzuki-Miyaura) for attaching aromatic functional groups or PROTAC warheads.
UPOR Biotech supplies two grades. Research / Pharma Intermediate Grade: ≥98% HPLC purity, ≥99% enantiomeric excess (ee) — suitable for discovery chemistry, lead optimization, medicinal chemistry, and PROTAC development. cGMP Grade: ≥99% HPLC purity, ≥99.5% enantiomeric excess (ee) — manufactured under ICH Q7 cGMP guidelines with full batch traceability, Type II DMF support, stability data (25°C/60%RH real-time and 40°C/75%RH accelerated), and complete batch manufacturing records. cGMP grade is suitable for IND-enabling GLP toxicology studies, clinical trial material (CTM) manufacturing, and commercial pharmaceutical production. Both grades include: COA with HPLC purity, chiral HPLC ee determination, residual solvents (ICH Q3C), heavy metals (≤10 ppm total, individual elements per USP <232>), microbial limits (USP <61>/<62>), MSDS, HPLC chromatogram, chiral HPLC chromatogram, NMR (¹H and ¹³C), and mass spectrum (ESI-MS or HRMS).
Storage: –20 °C ± 5 °C in a tightly sealed, moisture-proof container under inert gas (argon or nitrogen). The Boc protecting group is acid-labile: it is cleaved by TFA (20–50% in DCM, 1–4 h at room temperature), HCl/dioxane (4 M, 30 min–2 h), or formic acid. The compound is stable under basic and neutral conditions — compatible with Fmoc-SPPS (20% piperidine/DMF, DIC/HOBt or HBTU/HATU coupling, standard TFA cleavage cocktails). Boc stability in solution: DMF/DMSO stock solutions should be prepared fresh or stored at –20 °C for ≤1 week. Avoid: prolonged exposure to moisture (Boc hydrolysis), strong acids, and temperatures above 25 °C. Allow the sealed container to warm to ambient temperature before opening to prevent condensation. Under recommended storage, shelf life is 2 years from the date of manufacture.
Every shipment includes: COA (HPLC purity ≥98% or ≥99%, chiral HPLC ee ≥99% or ≥99.5%, full impurity profile, heavy metals ≤10 ppm, residual solvents per USP <467>/EP <5.4>/ICH Q3C, microbial panel per USP <61>/<62>), MSDS, HPLC Chromatogram, Chiral HPLC Chromatogram, NMR Spectrum (¹H 400 MHz and ¹³C 100 MHz), Mass Spectrum (ESI-MS or HRMS), BSE/TSE-Free Statement, Non-GMO Statement, Allergen Statement, HALAL Certificate, KOSHER Certificate, ISO 22000 + HACCP, ISO 9001:2015, FDA Facility Registration, Stability Data (cGMP grade: 25°C/60%RH real-time 24-month and 40°C/75%RH accelerated 6-month), and Complete Lot Traceability. cGMP grade additionally includes Type II DMF Letter of Authorization (upon signed CDA) and Batch Manufacturing Record summary. Free sample available for qualified B2B buyers. MOQ: 1 g (Research Grade), 100 g (cGMP Grade).