香港大学李学臣团队利用仿生树脂上合环脒生成全合成链胺嘧啶和克雷伯唑啉。相关研究成果发表在2024年6月24日出版的《德国应用化学》。

根据基因组挖掘结果，二酮哌嗪（DKP）衍生的环脒结构广泛存在于肽天然产物中。在很大程度上未知的生物活性和作用模式部分是由于通过微生物和化学方法获得的化合物较差。

为了应对这一挑战，该文中，研究人员开发了树脂上闭环脒形成策略，以合成含有N-末端DKP衍生的环脒结构的肽，其中通过HgCl₂激活硫代脒介导的6-外-三g环化是关键步骤。利用这一新策略，研究人员完成了链胺嘧啶和克雷伯唑啉的全合成。同时，合成了11个克雷伯唑啉类似物，用于结构-活性关系研究。

附：英文原文

Title: Total Syntheses of Streptamidine and Klebsazolicin Using Biomimetic On-Resin Ring-Closing Amidine Formation

Author: Shunhe Liu, Yang Tang, Sheng Chen, Xuechen Li, Han Liu

Issue&Volume: 2024-06-24

Abstract: Diketopiperazine (DKP) derived cyclic amidine structures widely exist in peptide natural products according to the genome mining result. The largely unknown bioactivity and mode of action are partially caused by the poor availability of the compounds via microbiological and chemical approaches. To tackle this challenge, in this work, we have developed the on-resin ring-closing amidine formation strategy to synthesize peptides containing N-terminal DKP derived cyclic amidine structure, in which the 6-exo-trig cyclization mediated by HgCl2 activation of thioamides was the key step. Leveraging from this new strategy, we finished the total syntheses of streptamidine and klebsazolicin. Meanwhile, eleven klebsazolicin analogues were synthesized for its structure-activity relationship study.

DOI: 10.1002/anie.202407952

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202407952