The most common strategy for the synthesis of amide bonds is the condensation of amines with carboxylic acids in the presence of carbodiimides, (EDC HCl, DIC, T-BEC). Carbodiimides react with the carboxylic group to render the highly reactive O-acylisourea (see scheme). Due to its high reactivity, O-acylisourea decomposes rapidly and/or undergoes rearrangement to form the totally inactive N-acylurea or in the case of the carbamate protected α-amino acids, it evolves to oxazolone, which shows poor reactivity and provokes the loss of chiral integrity. To mitigate this inefficiency in the carbodiimide-mediated coupling, a coupling additive such as OxymaPure®, HOBt, HOPO, or others can be added to the coupling cocktail. Since the active species formed shows increased stability, has excellent acylation capabilities, and significantly minimizes the side-reactions associated with  O-acylisourea.