Fmoc-Glu-OtBu

Fmoc-Glu-OtBu is a selectively protected building block widely utilized in Fmoc solid‑phase peptide synthesis for the introduction of glutamic acid residues into peptide sequences. Fmoc-Glu-OtBu is particularly valued for the preparation of γ‑glutamyl peptides, where the side‑chain carboxyl is involved in peptide‑like bonds, as well as for library synthesis applications where selective unmasking of protecting groups is required. In Fmoc-Glu-OtBu, the α‑amino group is protected by the base‑labile Fmoc group, while the side‑chain γ‑carboxyl is protected as an acid‑labile tert‑butyl ester. After condensation of the side‑chain carboxyl with an appropriate amine or alcohol, the γ‑amino and carboxyl functions can be selectively unmasked — with 20% piperidine in DMF removing the Fmoc group, and 50% TFA in DCM removing the tBu ester — facilitating the synthesis of complex peptide architectures. As a standard building block for Fmoc SPPS, Fmoc-Glu-OtBu is manufactured under quality level 200 and is fully compatible with both automated and manual peptide synthesis platforms.

Product Parameters

Quality Assurance at Cosperpharm

Each batch undergoes:

  Gas chromatography (GC) – purity ≥97.0%

  Non‑aqueous titration – purity ≥97.0%

  Refractive index – confirmatory analysis

  ¹H NMR – structural verification

  Appearance – colorless to light yellow to light orange clear liquid

A comprehensive COA, MSDS (with full GHS information), and certificate of origin accompany every shipment.

Synthetic Route

(1) Prepare a mixture of glutamic acid-5-tert-butyl ester (Glu(OtBu)) and glutamic acid-1-tert-butyl ester (Glu-OtBu): In a 2000 mL three-port flask, add 581 g tert-butyl acetate and 147 g glutamic acid, stir, gradually add 100 mL perchloric acid, react at 20°C for 48 hours, cool to 0°C, then add 600 mL water and neutralize with Na₂CO₃ to pH 8–9. Perform liquid separation, wash three times with 100 mL 1% Na₂CO₃ aqueous solution, combine the aqueous phases, and extract three times with 200 mL petroleum ether.

(2) Transfer the aqueous phase obtained from step (1) to a 2 L three-port flask, add 187.5 g CuSO₄·5H₂O, stir, adjust pH to 8–9 with sodium carbonate, add 100 mL tetrahydrofuran and 33.7 g Fmoc-OSu, maintain pH at 8–9, react for 8 hours to yield the crude product fluorene methoxycarbonyl-glutamic acid-1-tert-butyl ester. Acidify this crude product with HCl, extract with ethyl acetate, concentrate under reduced pressure, filter, and dry to obtain 36 g fluorene methoxycarbonyl-L-glutamic acid-1-tert-butyl ester. Analysis by HPLC showed the product's purity to be 99.1%, optical rotation-9.4 (c = 1, in HAc), melting point 109.5–110.6 °C, and isomer content 0.03%.

Application Scenarios

1.Fmoc Solid‑Phase Peptide Synthesis

As a standard building block for Fmoc SPPS, Fmoc-Glu-OtBu is used to incorporate L‑glutamic acid residues into synthetic peptides. It is fully compatible with automated and manual peptide synthesizers using standard Fmoc/tBu chemistry protocols.

2.γ‑Glutamyl Peptide Synthesis

Fmoc-Glu-OtBu is the key building block for the preparation of γ‑glutamyl peptides by Fmoc SPPS, where the side‑chain γ‑carboxyl is involved in peptide‑like bonds — a structural motif found in glutathione and other bioactive peptides.

3.Synthesis of Branched Peptides and Dendrimers

After condensation of the side‑chain carboxyl with an appropriate amine or alcohol, the protecting groups can be sequentially unmasked to synthesize branched esters, amides, lactams, and lactones containing the glutamyl unit — enabling the construction of peptide dendrimers and complex branched architectures.

4.Peptide Library Synthesis

Fmoc-Glu-OtBu is a key building block in combinatorial peptide library synthesis, enabling rapid, high‑throughput assembly of diverse peptide sequences for drug discovery and lead optimization programs.

5.Medicinal Chemistry & Drug Discovery

Fmoc-Glu-OtBu is widely used in medicinal chemistry as a building block for the synthesis of peptides and peptidomimetics, supporting drug discovery programs targeting a broad range of therapeutic areas including oncology, metabolic disorders, and central nervous system diseases.

6.Process Development & Scale‑Up

Process chemists use Fmoc-Glu-OtBu for reaction optimization, impurity mapping, and development of scalable manufacturing routes for therapeutic peptides. Cosperpharm provides characterization data and process support for seamless scale‑up from laboratory to pilot plant.

7.GMP Peptide Manufacturing

For contract manufacturing organizations and pharmaceutical companies producing therapeutic peptides under GMP, Fmoc-Glu-OtBu is supplied with full analytical documentation, including COA, stability data, and custom quality agreements to support regulatory submissions.

8.Branched Amide and Lactam Synthesis

The orthogonal protection strategy of Fmoc-Glu-OtBu facilitates the synthesis of branched amides and lactams — complex cyclic and bicyclic structures that are of interest in the development of constrained peptide therapeutics and bioactive natural product analogs.

Contact Us

Looking for a trusted supplier of Fmoc-Glu-OtBu for your peptide synthesis project? Cosperpharm offers high‑purity product with comprehensive documentation and flexible supply options — from gram quantities for early research to bulk volumes for commercial manufacturing. Reach out to our team for a quote or technical consultation.