Fmoc-Asp(OMpe)-OH

Fmoc-Asp(OMpe)-OH was introduced in 1996 as a new protecting group for aspartic acid that provides good protection against base‑catalyzed aspartimide formation in Fmoc solid‑phase peptide synthesis. The OMpe side‑chain protecting group in Fmoc-Asp(OMpe)-OH significantly reduces aspartimide formation, an undesired side‑chain reaction encountered with the repetitive piperidine treatment needed for Fmoc removal. The bulky OMpe protecting group in Fmoc-Asp(OMpe)-OH offers considerably more protection against the formation of aspartimide‑related by‑products than the commonly used OtBu group, as documented in the primary literature. Fmoc-Asp(OMpe)-OH is an excellent derivative for minimizing aspartimide formation during Fmoc SPPS of Asp‑containing peptides, and is particularly useful for peptide sequences featuring DG, DN, DS, and DT motifs where aspartimide formation is most problematic.

Product Parameters

Why Cosperpharm?

When problematic peptide sequences — especially those containing DG, DN, DS, or DT motifs — are causing aspartimide‑related purification failures, Cosperpharm delivers Fmoc-Asp(OMpe)-OH as the proven solution.

A solution to the aspartimide problem. Aspartimide formation during Fmoc SPPS can lead to batch rejection, purification failures, and extended development timelines. Fmoc-Asp(OMpe)-OH was specifically designed to address this challenge, offering significantly better protection than the standard OtBu group. Research has documented 3‑fold reduction in D‑Asp epimerization (from 18% to 6%) in Asp‑Gly motifs when using OMpe protection compared to OtBu, as well as reduced aspartimide decay per cycle.

Documentation that supports your process development. Each shipment of Fmoc-Asp(OMpe)-OH includes a Certificate of Analysis (COA) with batch‑specific HPLC purity (≥98.0%), enantiomeric purity (≥99.5%), optical rotation verification, melting point data, and identity confirmation. For customers engaged in cGMP peptide manufacturing, Cosperpharm provides enhanced documentation packages, stability data, and custom quality agreements upon request.

Flexible supply from discovery to commercial production. Cosperpharm supplies Fmoc-Asp(OMpe)-OH across the full range of applications — from 1 g for sequence optimization and process development, to 5 g–25 g for pilot batches, to larger quantities for commercial peptide manufacturing. R&D samples ship within 5–7 business days; bulk orders ship within 2–3 weeks.

Technical support for sequence‑specific challenges. Our process chemistry team can advise on coupling strategies for sequences where aspartimide formation is most problematic, recommend appropriate coupling reagents and deprotection protocols, and help optimize conditions for peptides containing multiple Asp residues. Because we understand that Fmoc-Asp(OMpe)-OH is not just a building block — it is a solution to a specific synthetic challenge.

Direct OtBu replacement — no protocol changes needed. Fmoc-Asp(OMpe)-OH can be used as a direct substitute for Fmoc‑Asp(OtBu)‑OH without requiring modifications to existing SPPS protocols. This enables seamless integration into validated synthesis workflows, minimizing process development time.

Global reach with transparent pricing. Cosperpharm ships to peptide manufacturers, CROs, and pharmaceutical companies worldwide, with full customs documentation included. Volume discounts apply, and we communicate lead times upfront.

Product Advantages

1. OMpe Protecting Group: Superior Aspartimide Suppression

The OMpe (O‑3‑methylpent‑3‑yl) side‑chain protecting group in Fmoc-Asp(OMpe)-OH was specifically designed to address base‑catalyzed aspartimide formation during repetitive piperidine treatments in Fmoc SPPS. Compared to the standard OtBu group, the bulky, branched OMpe ester provides significantly greater steric shielding of the β‑carboxyl carbonyl, preventing nucleophilic attack by the preceding amide nitrogen that initiates aspartimide cyclization. This results in cleaner crude product and higher overall yields for Asp‑containing peptides.

2. Direct Replacement for Fmoc-Asp(OtBu)-OH

Fmoc-Asp(OMpe)-OH can be used as a direct substitute for Fmoc‑Asp(OtBu)‑OH in standard SPPS workflows without any protocol modifications. The OMpe group is removed under standard TFA cleavage conditions, making integration into existing processes seamless. This eliminates the need for re‑optimization, saving time and resources.

3. Targeted for Problematic Sequence Motifs

Fmoc-Asp(OMpe)-OH is particularly useful for peptide sequences featuring DG, DN, DS, and DT motifs — the sequences where aspartimide formation is most prevalent and problematic. For multi‑Asp sequences, the benefits of OMpe protection are even more pronounced, with documented reductions in D‑Asp epimerization and aspartimide decay per cycle.

4. High Chiral Purity Guaranteed

With guaranteed enantiomeric purity ≥99.5%, Fmoc-Asp(OMpe)-OH ensures that the stereochemical integrity of the aspartic acid residue is maintained throughout synthesis. This is critical for the production of therapeutic peptides where even low levels of D‑amino acid impurities can significantly impact biological activity and safety.

5. Compatible with Standard Coupling Reagents

Fmoc-Asp(OMpe)-OH is fully compatible with standard coupling reagents used in Fmoc SPPS, including HBTU, HATU, DIC, and PyBOP. The steric bulk of the OMpe group does not interfere with coupling efficiency, making it a practical solution for routine peptide synthesis.

Synthetic Route

Preparation as a New Protecting Group for Aspartic Acid

Fmoc-Asp(OMpe)-OH was first described in 1996 by Karlström and Undén as a new protecting group for aspartic acid designed to minimize piperidine‑catalyzed aspartimide formation in Fmoc SPPS.

The synthetic approach involves the selective esterification of the β‑carboxyl group of Fmoc‑aspartic acid with the sterically hindered 3‑methylpentan‑3‑ol (also referred to as 3‑methyl‑3‑pentanol or ethyl methyl ethyl carbinol). The reaction typically employs a coupling reagent such as DCC or EDC along with a catalyst like DMAP to facilitate ester formation. After purification, the product is obtained as a solid with the OMpe protecting group intact at the β‑position, while the α‑carboxylic acid remains free for subsequent SPPS coupling.

Contact Us

Is aspartimide formation compromising your Asp‑containing peptide synthesis? Contact Cosperpharm today to order Fmoc-Asp(OMpe)-OH — the proven solution for suppressing base‑catalyzed aspartimide formation in Fmoc SPPS.

Our team is ready to assist with quotes, technical support, custom packaging, and enhanced documentation for regulatory filings. Reach out to us — we look forward to helping you synthesize cleaner peptides.