HOBt

HOBt, or 1-hydroxybenzotriazole, is an organic compound used as a coupling additive in peptide synthesis and related amide bond-forming reactions. It is valued for its ability to suppress racemization of chiral centers and to improve coupling yields when used with carbodiimide activators.

Mechanism: In carbodiimide-mediated activation, carboxyl groups form reactive O-acylurea intermediates. HOBt reacts with this intermediate to form a more stable O-benzotriazole ester (an OBt active ester). This species reacts with amines to give amide bonds efficiently while minimizing side reactions such as racemization via oxazolone formation.

Applications and related reagents: HOBt is widely used in solid-phase and solution-phase peptide synthesis, often in combination with DCC or DIC or EDC. Derivatives such as HOAt (1-hydroxy-7-azabenzotriazole) and modern uronium-based reagents (e.g., HATU, HBTU) have been developed to further improve coupling efficiency and further reduce racemization.

Safety and handling: HOBt and some of its salts can be explosive when dry, and should be handled with care under appropriate safety guidelines. Hydrated forms are generally safer to handle; use proper containment to minimize dust and static hazards.