TSTU

TSTU is a coupling reagent used to prepare activated hydroxysuccinimide (-Osu) esters in situ. It can be used to activate carboxyl compounds either in organic solvents or in the presence of water, thus making it useful for coupling hydrophilic compounds. α-Substituted carboxylic acids, such as α-amino acids, can produce problems when activated in the presence of water, so it is recommended that these compounds be activated in a water-free solvent, and then coupled in a mixed aqueous/organic solvent.

 Coupling with TSTU in Aqueous Solvent Mixtures1 

1. Dissolve the acid in a 2:2:1 mixture of DMF/dioxane/water. 

2. Add 3 equivalents of diisopropylethylamine and 1.3 equivalents of TSTU. 

3. After the formation of the -OSu ester is complete, add 1.5 equivalents of the amine. 

4. After the reaction is complete, the solvents are removed and the crude product is isolated.