COMU | CAS 1075198-30-9 | ≥98%

Next-generation peptide coupling reagent — COMU is a uronium-type coupling reagent developed by Albericio and co-workers as a superior alternative to established reagents such as HBTU, HATU, and TBTU. It combines the Oxyma leaving group (ethyl 2-cyano-2-(hydroxyimino)acetate) with a morpholinium uronium cation, delivering fast and efficient amide bond formation with minimal racemisation. COMU was first reported in 2009 and has since been adopted in both academic and industrial peptide synthesis (El-Faham and Albericio, J. Pept. Sci. 2010, 16, 6).

Solid-phase peptide synthesis (SPPS) — COMU is widely used in Fmoc-SPPS for the assembly of peptides and small proteins. It offers coupling rates comparable to HATU at significantly lower cost and without the explosion risk associated with HOBt-based reagents. Coupling reactions with COMU typically reach completion within minutes at room temperature using DIEA or collidine as base in DMF. It is particularly effective for sterically hindered amino acids and for double couplings of difficult sequences where HBTU gives incomplete conversion.

Solution-phase amide bond formation — COMU is an efficient coupling reagent for solution-phase amide synthesis, including the preparation of pharmaceutical intermediates, peptidomimetics, and macrocyclic peptides. Its high solubility in DMF and NMP, combined with rapid activation kinetics, makes it suitable for both small-scale medicinal chemistry and process-scale applications.

Non-explosive safety profile — a key advantage of COMU over HOBt- and HOAt-based coupling reagents is its classification as non-explosive. COMU contains the Oxyma leaving group instead of hydroxybenzotriazole, eliminating the friction- and impact-sensitivity hazards that have led to shipping restrictions and safety incidents with HOBt and reagents derived from it. This makes COMU the preferred coupling reagent in industrial environments where safety regulations prohibit the storage and handling of explosive materials (Subirós-Funosas et al., Chem. Eur. J. 2009, 15, 9394).

Low racemisation — COMU consistently delivers among the lowest levels of epimerisation reported for uronium coupling reagents. In comparative studies using standard racemisation test models (e.g., Z-Phg-Pro-NH₂ or the Young test), COMU outperforms HBTU and matches or exceeds HATU in preserving chiral integrity at the activated amino acid centre. This property is critical for the synthesis of peptides containing configurationally labile residues such as cysteine, histidine, and phenylglycine.

Segment condensation and fragment coupling — COMU has been successfully applied to the condensation of protected peptide fragments in convergent synthesis strategies. Its rapid activation and low epimerisation make it well suited for joining large fragments where prolonged reaction times or excess reagent would promote side reactions.

Amide bond formation beyond peptides — beyond peptide chemistry, COMU has been used for the synthesis of amide-containing pharmaceutical intermediates, polymer functionalisation via amide linkages, and the preparation of prodrug conjugates. Its compatibility with a range of carboxylic acids and amines, including secondary amines and anilines, broadens its utility as a general-purpose amide coupling reagent in organic synthesis.