Highly Efficient Coupling of Sterically Hindered Amino Acids to H-Pro-CTC Resin under Microwave Irradiation

Under microwave irradiation, five sterically hindered amino acids were coupled to H-Pro-CTC resin (CTC resin, 2-chlorotrityl chloride resin) in a novel solid-phase peptide synthesis (SPPS) reactor, severally. The triple coupling method was carried out using DMF/NMP/THF (V : V : V= 1 : 1 : 1), NMP/DMSO/THF (V : V : =4 : 1 : 1), DMF/DMSO/THF (V : V V=4 : 1 : 1) as solvent. The optimal conditions including coupling reagent, concentration of amino acids, microwave irritation time, reaction temperature and maintaining time were HBTU, 7 mmol/L, 3 min, 35 °C and 3 min for every coupling, respectively. Compared with the conventional method which was not microwave-assisted, the excess of sterically hindered amino acids decreased from 5-fold to 2-fold and the coupling reaction rate increased by over 16 times. The coupling yields of the five sterically hindered amino acids to H-Pro-CTC resin were all improved to over 80%.