فهرست نشریات علمی دسترسی آزاد ایران

A highly efficient and sustainable Continuous Flow Liquid Phase Peptide Synthesis (CF-LPPS) approach is reported, assisted with a fluoride-sensitive hydrophobic tag 2-phenyl-2-(trimethylsilyl) ethan-1-ol (PTMSE). Using this method, we solved the problem of solid-phase peptide synthesis consuming large amounts of solvent, which is neither environmentally friendly nor green. The continuous flow system consists of three parts, namely a coupled unit (microchannel reactor), a deprotection unit (packed bed reactor), and a washing and extraction unit (microchannel mixer), where the washing and extraction units need to be carried out twice, after the coupling unit and after the deprotection unit. We use PTMSE as a hydrophobic tag for the C-terminal, continuously repeating the coupling reaction, washing and decontamination process, deprotection reaction, and washing and decontamination process in a continuous flow system until the target peptide chain is synthesized. Using this method, we successfully synthesized palmitoyl peptides. In this approach, the greener solvent ethyl acetate is employed as a substitute for undesirable DMF, and Cbz-protected amino acids with clean deprotection are adopted as opposed to piperidine (a regulated chemical reagent), Fmoc-deprotection. Using this system, high-purity palmitoyl peptides (> 95% purity) were synthesized in an environmentally friendly way. The purity of palmitoyl pentapeptide reached 97.5%, while the purity of palmitoyl hexapeptide reached 96.3%.In addition, during the synthesis of PTNSE, a safer anhydrous methyl tert-butyl ether is used to replace the previously reported anhydrous diethyl ether. This method is both relatively safe and relatively reliable. This method provides a green and promising strategy for the efficient synthesis of peptides.