| HS Code | 908272 |
| Product Name | Fmoc-L-Glutamine |
| Cas Number | 71989-20-3 |
| Molecular Formula | C20H20N2O5 |
| Molecular Weight | 384.38 g/mol |
| Purity | ≥98% |
| Appearance | White to off-white powder |
| Storage Conditions | Store at -20°C, protected from light, under inert atmosphere |
| Solubility | Soluble in DMSO and DMF; sparingly soluble in water |
| Applications | Peptide synthesis, solid-phase peptide synthesis (SPPS) |
| Synonyms | Fmoc-Gln-OH; N-alpha-Fmoc-L-glutamine |
| Melting Point | 188-190°C (dec.) |
| Mdl Number | MFCD00065559 |
As an accredited Fmoc-L-Glutamine factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Fmoc-L-Glutamine, 5 g, packaged in an amber glass vial with a tight-seal cap, under nitrogen, with desiccant. |
| Container Loading (20′ FCL) | Fmoc-L-Glutamine packed in sealed drums, palletized, secured for 20′ FCL shipment, protected from moisture and temperature extremes. |
| Shipping | Fmoc-L-Glutamine ships at ambient temperature in a sealed, light-resistant container with desiccant. It is stable under normal transport conditions but should be kept away from moisture, heat, and prolonged light exposure. Upon receipt, store refrigerated (2–8°C) in a tightly closed container, and handle using standard laboratory PPE. |
| Storage | Store Fmoc-L-Glutamine in a tightly sealed container, protected from light, in a cool, dry place. For long-term stability, refrigeration at –20°C is recommended. Avoid exposure to moisture, heat, and repeated freeze-thaw cycles. Handle under inert gas if possible. Keep container desiccated and allow to warm to ambient temperature before opening to prevent condensation. |
| Shelf Life | Shelf life is typically 2 years when stored at -20°C, protected from light and moisture, in a tightly sealed container. |
Within multi-kilogram solid-phase peptide synthesis trains operating under full ICH Q7 quality systems, Fmoc-L-Glutamine is introduced as the Nα-protected building block for Gln residues in therapeutic peptide sequences. Raw-material acceptance criteria applied in GMP peptide API manufacture include assay by HPLC ≥98.0%, enantiomeric purity ≥99.5%, loss on drying ≤0.5%, and single unknown impurity ≤1.0%; residual solvents are controlled to USP <467> limits, elemental impurities to ICH Q3D Option 1 daily exposure values, and nitrosamine risk assessed under ICH M7 when secondary amine deprotection is used downstream. In automated peptide synthesizers with 1–10 L glass bubble-column or stirred-vessel reactors, the resin is swelled in DMF at 10–15 mL/g resin mass. Fmoc-L-Glutamine is dissolved in DMF at 0.2–0.4 M and activated with HBTU/HOBt/DIPEA at a molar ratio of 4:4:4:8 relative to resin amine substitution. When the sequence requires suppression of side-chain amide dehydration or when coupling is performed at a jacket temperature above 25°C, HATU/Oxyma/DIPEA at 3:3:3:6 is substituted. Coupling completion is checked by Kaiser or TNBS free-amine testing, and a recoupling cycle is triggered if residual free amine remains above 2.0%. Fmoc deprotection uses 20% piperidine in DMF for 5–10 min, followed by DMF washes. The assembled peptide chain is cleaved with TFA/TIS/water 95:2.5:2.5, precipitated in cold MTBE, purified by reversed-phase preparative HPLC on C18 media with acetonitrile/water gradients, converted to acetate or hydrochloride salt, and lyophilized. Terminal product types include therapeutic peptide active pharmaceutical ingredients and lyophilized peptide acetate intermediates for metabolic, endocrine, and oncology development programs.
At pilot scale, the primary process conflict is not initial dissolution but on-resin chain aggregation arising from unprotected Gln side-chain amide hydrogen bonding when two or more Gln/Asn residues are present. In 50–500 mL polypropylene reactors attached to a CEM Liberty Blue or Biotage Alstra synthesizer, the resin substitution is maintained at 0.3–0.5 mmol/g to reduce interchain proximity. Fmoc-L-Glutamine is metered as a 0.3 M DMF solution; the manufacturer’s recommended addition ratio is 3–5 equivalents relative to free amine. Published pilot data for this unprotected side-chain derivative indicate that coupling yields can drop below 85% when the sequence length exceeds 15–20 residues without chaotropic additives or backbone protection. To mitigate collapse, DMF is supplemented with 6–8% v/v ethylene carbonate or 10% v/v DMSO, and the vessel temperature is ramped to 50°C for two microwave coupling cycles of 5 min each. Critical process parameters include activator type, equivalents, preactivation time of 2–3 min, and deprotection temperature. Compliance for this pilot manufacture follows ISO 9001:2015 quality management and ICH Q2(R1) analytical validation principles; if the batch is later used for toxicology supply, ICH Q7 sections on raw material identity and traceability apply. The terminal product type is research-grade lyophilized peptide acetate or TFA salt for epitope mapping, selectivity profiling, and preclinical candidate validation.
| Process scale | Resin substitution | Fmoc-Gln-OH addition ratio | Activation system | Coupling condition | Residual free amine after double coupling |
|---|---|---|---|---|---|
| 0.1 mmol plate | 0.5 mmol/g | 4 eq | HBTU/HOBt/DIPEA 4:4:8 | 25°C, 60 min | <2.0% |
| 1 mmol microwave | 0.4 mmol/g | 4 eq | HATU/Oxyma/DIPEA 3:3:6 | 50°C, 2×5 min | <1.5% |
| 10 mmol pilot vessel | 0.35 mmol/g | 3.5 eq | HCTU/DIPEA | 30°C, 45 min | <2.0% |
Operational boundaries include exclusion of carbodiimide-based activators with unprotected Gln above 25°C because carbodiimide activation can dehydrate the side-chain amide to nitrile, and storage must be at 2–8°C under desiccant to prevent moisture uptake. The protected form Fmoc-Gln(Trt)-OH is recommended when sequences exceed 20 residues or when three consecutive Gln residues are present; published data for production-scale unprotected Fmoc-L-Glutamine are limited, so process characterisation should rely on Fmoc-release UV monitoring at 290 nm after deprotection.
Because high-throughput hit-to-lead programmes require parallel peptide library synthesis without individual activation optimisation, Fmoc-L-Glutamine is applied in 24-well or 96-well plate synthesizers as a standard Gln building block. The addition ratio is fixed at 4 equivalents relative to resin substitution in each well, with activation by HCTU and DIPEA in NMP at 0.2 M. The production process uses Teflon-frit plates on a vacuum manifold; after Fmoc removal with 20% piperidine/DMF and alternating DMF and DCM washes, side-chain deprotection and cleavage are performed with TFA/TIS/H2O 95:2.5:2.5. Crude peptides are lyophilized and desalted by C18 solid-phase extraction to remove non-peptide byproducts. Compliance for such research-use peptide libraries is aligned to ISO 9001:2015 and the non-GMP provisions of ICH Q11 where intermediates feed candidate selection. Terminal product types are crude or desalted peptide libraries in 96-well plates or single vials with open-access analytical reports.
Manufacture of short-chain protected peptide fragments via solution-phase chemistry uses Fmoc-L-Glutamine as an Nα-protected carboxy component activated as p-nitrophenyl ester or mixed anhydride. In a glass-lined reactor under nitrogen, the derivative is dissolved in THF at 5–10°C, treated with isobutyl chloroformate and N-methylmorpholine; the molar ratio of Fmoc-L-Glutamine to amino component is maintained at 1.05–1.20 equivalents. The coupling is typically completed within 1–2 h, after which the organic phase is washed with cold 0.1 M hydrochloric acid and 5% sodium bicarbonate. Side-chain deprotection is controlled by TFA-based cocktails, and the product is isolated by crystallization from ethyl acetate/hexane or by silica gel chromatography. Compliance standards include ICH Q11 for starting material definition and REACH registration for import quantities above 1 tonne per annum under EC 1907/2006. End products are isolated as protected dipeptide or tripeptide intermediates for subsequent SPPS chain extension or for incorporation into semi-synthetic peptide APIs. Published data for this specific configuration are limited; batch records should therefore include in-process HPLC monitoring at 210 nm for intermediate stability.
Peptide conjugate intermediates that carry a C-terminal lysine or cysteine for payload attachment are assembled using Fmoc-L-Glutamine as the Gln source when the side-chain amide must remain unblocked during final acidolysis. The addition ratio is set to 4 equivalents relative to resin amine, activated with HATU/DIPEA in DMF; coupling is performed at 25°C for 45 min with nitrogen agitation. The production process includes solid-phase peptide synthesis, on-resin cyclization or disulfide formation where required, TFA cleavage, and RP-HPLC purification to ≥95.0% purity. Compliance is assessed against ICH Q7 when the conjugate is intended as a drug substance intermediate, and against ICH Q3D for elemental impurities; if the conjugate is later formulated as a sterile injectable, 21 CFR 210/211 applies to finished drug product operations. Isolated materials are supplied as protected peptide-linker intermediates for peptide-drug conjugates or peptide-radiometal chelator conjugates for diagnostic use. The unprotected Gln side chain is kept under strictly anhydrous conditions during coupling to avoid pyroglutamate formation.
Under ISO 22716:2007 and the EFfCI GMP standard, cosmetic peptide active ingredients containing Gln residues are manufactured by solid-phase synthesis using Fmoc-L-Glutamine as the Gln source. The derivative is incorporated at 3–4 equivalents relative to resin loading, using DIC/Oxyma in DMF to minimize base-induced racemization. The production process includes sequential Fmoc deprotection with 20% piperidine/DMF, TFA cleavage, precipitation, and preparative HPLC; residual TFA is then reduced to ≤0.1% by ion exchange or by lyophilization from dilute hydrochloric acid. Final peptide actives are supplied as aqueous stock solutions preserved with phenoxyethanol or as lyophilized powders for skin care formulations. Residual solvent certificates are aligned to USP <467>, and the safety dossier for the finished cosmetic formula is prepared under EC 1223/2009. The final manufactured form is synthetic peptide ingredient for cosmetic serums, creams, and emulsions.
Competitive Fmoc-L-Glutamine prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please contact us at +8615365186327 or mail to admin@ascent-chem.com.
We will respond to you as soon as possible.
Tel: +8615365186327
Email: admin@ascent-chem.com
Flexible payment, competitive price, premium service - Inquire now!
Fmoc-L-glutamine, catalogue designation FMOC-GLN-OH, is the 9-fluorenylmethoxycarbonyl-protected (2S)-2,5-diamino-5-oxopentanoic acid derivative with CAS 71989-20-3, molecular formula C20H20N2O5, and formula weight 368.38 g/mol. The product is supplied as a white to off-white crystalline powder and is used as an Fmoc-protected amino acid derivative in solid-phase peptide synthesis (SPPS). Unlike Fmoc-L-glutamine(trityl)-OH, the side-chain primary amide is not blocked; this reduces the molecular weight penalty per coupling and eliminates the need for trityl cation scavenging during acidic resin cleavage. Routine release documentation includes reversed-phase HPLC purity ≥98.5% area, loss on drying ≤0.5%, and specific rotation within −17° to −19° (c = 1 in DMF). The material is typically filled into amber glass bottles under nitrogen and stored at 2–8 °C in a desiccated environment. When the product is specified for active pharmaceutical ingredient manufacture, elemental impurity testing is performed according to ICH Q3D limit thresholds.
Automated SPPS protocols for Fmoc-L-glutamine frequently use aminium or phosphonium activators in polar aprotic media. A representative loading solution consists of 0.2 mol/L Fmoc-L-glutamine in DMF, 0.5 mol/L HATU, and 1.0 mol/L N,N-diisopropylethylamine, delivered at 4–8 molar equivalents relative to resin substitution. On a 0.25 mmol scale using a polystyrene-1% divinylbenzene resin with substitution 0.4 mmol/g, the coupling volume is set to 2.5 mL per 0.1 mmol resin, providing a 0.2 mol/L Fmoc-L-glutamine concentration after mixing. Preactivation is held at 20–25 °C for 2–5 min before transfer to the resin. Under these conditions, the unprotected side-chain amide is generally inert; however, carbodiimide-only activation without an auxiliary nucleophile such as HOBt or HOAt can convert the primary amide to the corresponding nitrile during extended activation. Published kinetic data for this specific dehydration on Fmoc-L-glutamine is limited; process controls therefore restrict preactivation time to ≤15 min when HBTU or HATU is used. Coupling efficiency is monitored by Kaiser or TNBS resin tests, with incomplete couplings typically receiving a second activation at 50–60 °C for 20 min on microwave-equipped synthesizers. Single coupling efficiencies greater than 99% are targeted; sequences that fall below this threshold after two activation cycles are terminated and resynthesized with an alternative protection strategy. The product is compatible with standard Fmoc deprotection using 20% piperidine in DMF for 3–10 min at ambient temperature; cumulative piperidine contact beyond 30 min is unnecessary and can promote diketopiperazine formation at terminal dipeptide sequences in a sequence-dependent manner. Production-scale batch records from automated synthesizers with 20 L glass reactors indicate that incomplete dissolution of Fmoc-L-glutamine in DMF at loadings above 0.3 mol/L can produce transient turbidity, resulting in inconsistent delivery through polytetrafluoroethylene transfer lines. Adding the solid to prewarmed DMF at 25–30 °C under nitrogen reduces this bottleneck.
Release documentation for commercial batches conforms to supplier certificate-of-analysis templates that include reversed-phase HPLC at 220 nm, thin-layer chromatography using chloroform/methanol/acetic acid 90:10:3, water content by Karl Fischer coulometry according to USP <921> with acceptance ≤0.5%, and residual solvent limits assigned under ICH Q3C. N,N-dimethylformamide, a class 2 solvent, is controlled to a permitted daily exposure of 8.8 mg/day; dichloromethane and acetonitrile are class 2 solvents with permitted daily exposures of 6.0 mg/day and 4.1 mg/day, respectively. Headspace gas chromatography-mass spectrometry is used for quantitation of residual DMF, dichloromethane, and acetonitrile in GMP peptide manufacturing. Enantiomeric purity is verified by chiral HPLC or by specific rotation, with acceptance typically ≥99.0% enantiomeric excess. Thermal stability screening by simultaneous differential scanning calorimetry and thermogravimetric analysis shows decomposition onset near 220–225 °C; published data for this specific configuration is limited. Batch-to-batch variation in residual DMF has been observed between drum quantities dried in static tray ovens and those processed in rotary evaporators at 40 °C. GMP peptide manufacturers re-qualify material by Karl Fischer and headspace gas chromatography before use in active pharmaceutical ingredient campaigns. Pre-drying at 25 °C in a vacuum oven at ≤10 kPa for 4 h is applied when the material has been stored above 60% relative humidity or when gravimetric lot checks exceed 0.5% moisture. On automated peptide synthesizers operating at 0.1 mmol to 50 mmol scale, the free-flowing powder is dispensed directly from solid-phase hoppers after breaking aggregates by sieving through a 500 μm mesh.
Storage conditions for Fmoc-L-glutamine are established by the lability of the Fmoc group toward bases and by the hygroscopic character of the free amide. The product is stored inside desiccated cold storage at 2–8 °C and protected from ultraviolet light because the fluorenylmethyl chromophore undergoes photolytic cleavage at trace levels. Contact with piperidine, amines, or alkaline aqueous buffers must be avoided before coupling because the Fmoc group is removed under these conditions. Aqueous workups at pH >7.5 are not used for post-coupling solutions. The derivative is soluble in DMF and N-methyl-2-pyrrolidone at concentrations up to 0.4 mol/L at 25 °C; solubility in dichloromethane is limited and is not relied upon for transfer operations. Process-scale dissolution in DMF is performed under nitrogen with slow overhead stirring at 120–150 rpm in glass-lined vessels, followed by filtration through a 0.45 μm polytetrafluoroethylene membrane before use in GMP peptide synthesizers. Long-term storage beyond 24 months from the certificate-of-analysis date is not recommended unless re-testing is performed according to the original specification. Exposure to atmospheric moisture above 60% relative humidity during dispensing has been associated with particle aggregation and off-specification Karl Fischer results in tropical production environments.
Comparative evaluation against side-chain-protected glutamine derivatives on production-scale synthesizers shows that the unprotected amide is preferred when the target peptide contains a single glutamine residue remote from aggregation-prone sequences. Fmoc-L-glutamine provides a lower molecular weight intermediate than Fmoc-L-glutamine(trityl)-OH, eliminating the need for triisopropylsilane in the cleavage cocktail for that residue; however, the unprotected amide is not selected for sequences requiring extensive chain elongation at elevated temperature if solubility of the protected peptide-resin is already poor. Fmoc-L-glutamic acid-gamma-tert-butyl ester is not a direct replacement because it introduces a carboxylic acid side chain rather than an amide; it is selected when subsequent side-chain modification at the gamma-position is required. Fmoc-D-glutamine differs only in stereochemistry and is held to the same release limits with chiral HPLC acceptance inverted to the D-enantiomer. The governing variables in substitution are shown in the following table.
| Attribute | Fmoc-L-glutamine | Fmoc-L-glutamine(trityl)-OH | Boc-L-glutamine |
|---|---|---|---|
| Side-chain amide protection | None | Trityl | None |
| Molecular formula | C20H20N2O5 | C39H34N2O5 | C10H18N2O5 |
| Formula weight | 368.38 g/mol | 610.70 g/mol | 246.26 g/mol |
| Final acidic cleavage requirement | TFA-based cocktail without trityl scavenger for this residue | TFA plus triisopropylsilane to capture trityl cation | HF or TFA-based strong acid cleavage in Boc SPPS |
| Orthogonal deprotection compatibility | Fmoc/tBu SPPS | Fmoc/tBu SPPS | Boc/benzyl SPPS |
| Typical use | Short to medium Gln-containing peptides | Long or aggregation-prone sequences | Boc SPPS of difficult sequences requiring strong acid cleavage |
Substitution of Fmoc-L-glutamine for Fmoc-L-glutamine(trityl)-OH in a given sequence is evaluated by trial couplings on 0.1 mmol resin samples and by liquid chromatography-mass spectrometry crude purity at the glutamine site. Industrial peptide manufacturers use this side-by-side comparison to avoid the increased steric hindrance of trityl in sterically congested coupling sites while retaining the solubility advantage of trityl in hydrophobic sequences. Published data for this specific configuration is limited; the selection is therefore made on a sequence-by-sequence basis.
Long-sequence syntheses that consider replacement of Fmoc-L-glutamine(trityl)-OH with the unprotected amide derivative require evaluation of resin-bound intermediate solubility and aggregation. Fmoc-L-glutamine is introduced into sequences of up to 40–50 amino acids when glutamine is located in solvent-exposed positions and when resin substitution is maintained between 0.2 mmol/g and 0.5 mmol/g. At higher substitution or in sequences containing polyglutamine or polyasparagine repeats, the unprotected amide can contribute to interchain hydrogen bonding, reduced swelling in DMF, and slower deprotection. These operational boundaries are evaluated by resin swelling measurements and by continuous-flow UV monitoring at 304 nm during piperidine Fmoc removal; absorbance decay beyond the standard 3–10 min window indicates restricted diffusion. In such cases, the trityl-protected derivative is retained or a pseudoproline dipeptide is inserted to break secondary structure. The unprotected derivative is not combined with carbodiimide-mediated C-terminal activation at elevated temperature in the absence of HOBt or HOAt because the nitrile side product has been observed in resin-bound crude liquid chromatography-mass spectrometry as a mass shift of −18 Da relative to the expected glutamine residue. This incompatibility is documented in route-scouting reports for pharmaceutical peptide active pharmaceutical ingredients and is managed by restricting activation protocols to aminium/HOBt or HATU/HOAt systems.
