ARTICLE

Liquid-Phase Synthesis of Peptide Alcohol Assisted by a Hydrophobic Silica-Based Tag

  • Cheng Rong ,
  • Qian Yiyi ,
  • Xu Yuanqiang ,
  • Su Xianbin
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  • NanJing Tech University,Nan Jing,210000

Received date: 2025-04-17

  Revised date: 2025-05-04

  Online published: 2025-06-19

Abstract

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.

Cite this article

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, 0 : 202503021 -202503021 . DOI: 10.6023/cjoc202503021

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