微波作用下大位阻氨基酸与H-Pro-CTC树脂的高效缩合

微波反应下, 运用新型固相肽合成反应器, 深入研究了五种大位阻氨基酸与H-Pro-CTC树脂(CTC树脂, 2-氯三苯甲基氯树脂)的缩合反应. 使用三次缩合的策略, 分别在DMF/NMP/THF (V∶V∶V＝1∶1∶1), NMP/DMSO/THF (V∶V∶V＝4∶1∶1), DMF/DMSO/THF (V∶V∶V＝4∶1∶1)混合溶剂中缩合一次, 每次缩合反应的最优条件为: 缩合试剂HBTU、氨基酸浓度7 mmol/L、微波辐射3 min、反应温度35 ℃、维持时间3 min, 与传统方法相比, 氨基酸的用量大大减少, 其过量倍数从5倍降低为2倍, 缩合反应速率提高了16倍以上. 五种大位阻氨基酸与H-Pro-CTC树脂的缩合率都提高到80%以上.

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∶V＝4∶1∶1), DMF/DMSO/THF (V∶V∶V＝4∶1∶1) as solvent. The optimal conditions in-cluding coupling reagent, concentration of amino acids, microwave irritation time, reaction temperature and maintaining time were HBTU, 7 mmol/L, 3 min, 35 ℃ 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%.