COMU: a safer and more effective replacement for benzotriazole-based uronium coupling reagents.
We describe a new family of uronium-type coupling reagents that differ in their iminium moieties and leaving groups. The presence of the morpholino group in conjunction with an oxime derivative--especially ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma)--had a marked influence on the solubilities, stabilities, and reactivities of the reagents. Finally, the new uronium salt derived from Oxyma (COMU) performed extremely well in the presence of only 1 equiv of base, thereby confirming the effect of the hydrogen bond acceptor in the reaction. COMU also showed a less hazardous safety profile than the benzotriazole-based HDMA and HDMB, which exhibited unpredictable autocatalytic decompositions. Furthermore, the Oxyma moiety contained in COMU suggests a lower risk of explosion than in the case of the benzotriazole derivatives.
El-Faham
Ayman
A
Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain. aymanel_faham@hotmail.com
Subirós Funosas
Ramon
R
Prohens
Rafel
R
Albericio
Fernando
F
D001372:Aza Compounds / Q000737:chemistry; D018360:Crystallography, X-Ray; D004076:Digoxigenin / Q000031:analogs & derivatives / Q000737:chemistry; D008968:Molecular Conformation; D009025:Morpholines / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011245:Pregnadienes / Q000737:chemistry; D013388:Succinimides / Q000737:chemistry; D014230:Triazoles / Q000737:chemistry*
C545908:(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)-dimethylamino-morpholinomethylene)methanaminium hexafluorophosphate; D001372:Aza Compounds; D009025:Morpholines; D009943:Organophosphorus Compounds; D010455:Peptides; D011245:Pregnadienes; D013388:Succinimides; D014230:Triazoles; C073892:N-hydroxysuccinimidyl digoxigenin-3-O-methylcarbonyl-epsilon-aminocaproate; C045419:oxyma; C012771:benzotriazole; C011852:1-hydroxybenzotriazole; D004076:Digoxigenin; C435757:1-hydroxy-7-azabenzotriazole