疏水性硅基标签辅助的肽醇液相合成

doi:10.6023/cjoc202503021

摘要/Abstract

本研究开发了一种新型疏水性硅基标签CBTBS(((氯亚甲基)双(1,4-亚苯基))双(氧))双(叔丁基二甲基硅烷)),用于辅助液相合成肽醇. 通过采用环境友好型溶剂乙酸乙酯(EA)替代具有生殖毒性的N,N-二甲基甲酰胺(DMF), 并使用3-巯基-1-丙烷磺酸钠(Mps)与1,8-二氮杂二环十一碳-7-烯(DBU)的协同脱保护体系(取代传统受管制的哌啶试剂). 该策略不仅能够高效且便捷地去除富烯加成物等副产物, 还实现了Gramicidin A片段的高效合成(粗品收率>80%). 与传统固相合成相比, 该方法的过程质量强度(PMI)大幅降低, 为肽醇的绿色合成开辟了一条高效、可持续的新途径.

关键词: 疏水性硅基标签, 肽醇, 液相合成, 绿色

This study presents the development of a novel hydrophobic silicon-based tag, CBTBS [((chloromethylene)bis(1,4-phenylene))bis(oxy))bis(tert-butyldimethylsilane)], for facilitating the liquid-phase synthesis of peptide alcohols. By replacing the reproductive-toxic solvent N,N-dimethylformamide (DMF) with the environmentally friendly ethyl acetate (EA) and implementing a synergistic deprotection system using sodium 3-mercapto-1-propanesulfonate (Mps) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (substituting the traditionally regulated piperidine reagent), this strategy enables efficient and convenient removal of byproducts such as fulvene adducts. Additionally, it achieves high-efficiency synthesis of the Gramicidin A fragment with a crude yield exceeding 80%. Compared with conventional solid-phase synthesis, this method significantly reduces the process mass intensity (PMI), thereby providing an efficient and sustainable new pathway for the green synthesis of peptide alcohols.

Key words: hydrophobic silica-based tag, peptide alcohol, liquid phase synthesis, green

引用此文

程蓉, 钱伊依, 徐元强, 苏贤斌. 疏水性硅基标签辅助的肽醇液相合成[J]. 有机化学, doi: 10.6023/cjoc202503021.

Cheng Rong, Qian Yiyi, Xu Yuanqiang, Su Xianbin. Liquid-Phase Synthesis of Peptide Alcohol Assisted by a Hydrophobic Silica-Based Tag[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202503021.

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