Solid-phase peptide synthesis under microwave power-temperature synergistic control

This study focuses on exploring the synergistic interaction effect between temperature fields and electromagnetic fields during microwave-assisted solid-phase peptide synthesis （SPPS）. A self-developed microwave irradiation–temperature control circulation system was employed to achieve precise regulation of both microwave power and reaction temperature. Under continuous microwave irradiation, the kinetics of peptide chain coupling and 9-fluorenylmethoxycarbonyl （Fmoc） deprotection were investigated, establishing optimal reaction durations （3.5 min for coupling and 2.5 min+2.5 min for deprotection）. Based on these parameters, a model system featuring a representative difficult sequence in SPPS was selected. The synthesis performance under three different heating modes—continuous microwave, pulsed microwave （duty cycle 0.6）, and conventional water bath—was compared under equivalent temperature conditions. The results demonstrated that continuous microwave irradiation significantly improves product purity and reduces the duration of key reaction steps by approximately 70%. These findings provide a novel engineering solution for the efficient synthesis of complex peptides.