OxymaPure Coupling Reagents: Beyond Solid-Phase Peptide Synthesis

Abstract

OxymaPure [ethyl 2-cyano-2-(hydroxyimino)acetate] is an exceptional reagent with which to suppress racemization and enhance coupling efficiency during amide bond formation. The tremendous popularity of OxymaPure has led to the development of several Oxyma-based reagents. OxymaPure and its derived reagents are widely used in solid- and solution-phase peptide chemistry. This review summarizes the recent developments and applications of OxymaPure and Oxyma-based reagents in peptide chemistry, in particular in solution-phase chemistry. Moreover, the side reaction associated with OxymaPure is also discussed.1 Introduction2 Oxyma-Based Coupling Reagents2.1 Aminium/Uronium Salts of OxymaPure2.2 Phosphonium Salts of OxymaPure2.3 Oxyma-Based Phosphates2.4 Sulfonate Esters of OxymaPure2.5 Benzoate Esters of OxymaPure2.6 Carbonates of OxymaPure Derivatives3 OxymaPure Derivatives4 Other Oxime-Based Additives and Coupling Reagents5 Side Reactions Using OxymaPure Derivatives6 Conclusion7 List of Abbreviations

Catalytic and Sustainable Amide Bond Formation using a DABCO/Dichlorotriazine System

“…[34] These methods have demonstrated cost-effectiveness and broad applicability. However, with the impressive number of recent reviews on sustainable amide synthesis progress, [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] it is clear that this topic is still of great importance, and there is an urgent need for new, environmentally-friendly approaches.…”

Amidation by reactive extrusion for the synthesis of active pharmaceutical ingredients teriflunomide and moclobemide

“…One of the mostly used is ethyl oxyma,‡ which was investigated in this study. 16 Finally, carbodiimides being sensitizing molecules, a carbodiimide-free oxyma-based coupling agent, COMU was also tested. 17…”

“…One of the mostly used is ethyl oxyma, ‡ which was investigated in this study. 16 Finally, carbodiimides being sensitizing molecules, a carbodiimide-free oxymabased coupling agent, COMU was also tested. 17 EDC.HCl, widely used together with DMAP as a base, in a catalytic amount, in solution or in solvent-free conditions, 4,9,10a,11e,f was investigated.…”

Speeding up sustainable solution-phase peptide synthesis using T3P® as a green coupling reagent: methods and challenges

“…More recently, Dunetz et al 25 confirmed prevention of racemization in T3P® mediated amide formation, selecting pyridine as the most suitable base. We explored herein the possibility to apply this reagent to continuous solution-phase synthesis, eliminating the need for other coupling reagents and carbodiimides, which display several disadvantages in terms of toxicity and safety, 26 aiming at developing a fast and green protocol for oligopeptide synthesis.…”

“…We explored, herein, the possibility of applying this reagent to continuous solution-phase synthesis, eliminating the need for other coupling reagents and carbodiimides, which display several disadvantages in terms of toxicity and safety, 26 to develop a fast and green protocol for oligopeptide synthesis.…”