An Atom-Economic Inverse Solid-Phase Peptide Synthesis Using Bn or BcM Esters of Amino Acids

Jian Li; Yue Zhu; Bo Liu; Feng Tang; Xing Zheng; Wei Huang

doi:10.1021/acs.orglett.1c02769

An Atom-Economic Inverse Solid-Phase Peptide Synthesis Using Bn or BcM Esters of Amino Acids

Org Lett. 2021 Oct 1;23(19):7571-7574. doi: 10.1021/acs.orglett.1c02769. Epub 2021 Sep 17.

Authors

Jian Li^{1

2

3}, Yue Zhu^{2

4}, Bo Liu^{1

2}, Feng Tang^{1

2

3}, Xing Zheng⁴, Wei Huang^{1

2

3}

Affiliations

¹ School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, Hangzhou 310024, China.
² CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
⁴ Group of Lead Compound, Department of Pharmacy, Hengyang Medicinal School, University of South China, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, Hunan 421001, China.

PMID: 34533312
DOI: 10.1021/acs.orglett.1c02769

Abstract

An atom-economic N-to-C-directed solid-phase peptide synthesis is reported that uses benzyl (Bn) or (benzhydryl-carbamoyl)-methyl (BcM) esters of amino acids as the building blocks, which facilitate efficient hydrazinolysis, convenient conversion to acyl azide, and robust amidation with the next amino acid ester. This method is free of coupling reagents and free of protection on the side-chain OH, CO₂H, CONH2, etc., therefore exhibiting a significantly improved atom economy compared to those of BOC- or Fmoc-based C-to-N-directed approaches.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / chemistry*
Esters
Indicators and Reagents / chemistry*
Molecular Structure
Peptides / chemical synthesis*
Peptides / chemistry
Solid-Phase Synthesis Techniques / methods

Substances

Amino Acids
Esters
Indicators and Reagents
Peptides