Nakahara Hiroki, Sennari Goh, Noguchi Yoshihiko, Hirose Tomoyasu, Sunazuka Toshiaki
Ōmura Satoshi Memorial Institute and Graduate School of Infection Control Sciences, Kitasato University 5-9-1 Shirokane, Minato-ku Tokyo 108-8641 Japan
Chem Sci. 2023 May 1;14(25):6882-6889. doi: 10.1039/d3sc01432k. eCollection 2023 Jun 28.
In the last couple of decades, technologies and strategies for peptide synthesis have advanced rapidly. Although solid-phase peptide synthesis (SPPS) and liquid-phase peptide synthesis (LPPS) have contributed significantly to the development of the field, there have been remaining challenges for C-terminal modifications of peptide compounds in SPPS and LPPS. Orthogonal to the current standard approach that relies on installation of a carrier molecule at the C-terminus of amino acids, we developed a new hydrophobic-tag carbonate reagent which facilitated robust preparation of nitrogen-tag-supported peptide compounds. This auxiliary was easily installed on a variety of amino acids including oligopeptides that have a broad range of noncanonical residues, allowing simple purification of the products by crystallization and filtration. We demonstrated a solid/hydrophobic-tag relay synthesis (STRS) strategy using the nitrogen-bound auxiliary for total synthesis of calpinactam.
在过去几十年中，肽合成技术和策略发展迅速。尽管固相肽合成（SPPS）和液相肽合成（LPPS）对该领域的发展做出了重大贡献，但在SPPS和LPPS中，肽化合物的C端修饰仍存在挑战。与目前依赖于在氨基酸C端安装载体分子的标准方法不同，我们开发了一种新型疏水标签碳酸酯试剂，该试剂有助于稳健地制备氮标签支持的肽化合物。这种辅助基团易于安装在各种氨基酸上，包括含有广泛非天然残基的寡肽，从而可以通过结晶和过滤对产物进行简单纯化。我们展示了一种使用氮结合辅助基团的固/疏水标签接力合成（STRS）策略用于卡尔皮内酰胺的全合成。
