Oral Presentation 8th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2022

  New Methods for Construction of Complex Peptide Macrocycles (#12)

Gong Chen 1
  1. State Key Laboratory of Elemento-organic Chemistry, Nankai University, China

Cyclic peptides have provided an important platform for exploration of biorelevant chemical space between small molecules and biologics. In comparison with the design and synthesis of small molecules, chemists’ ability to fine-tune the three-dimensional structures and properties of cyclic peptides lag behind. In this talk, we discuss our recent investigation of various chemical strategies, including metal-catalyzed, radial-mediated and classical polar reactions, for synthesis of peptide macrocycles with different structure features: 1) Construction of cyclophane-braced peptide macrocycles via palladium-catalyzed intramolecular arylation of various C-H bonds. 2) Streamlined construction of S-aryl ether linked peptide macrocycles via palladium-catalyzed intramolecular S-arylation in solution and on DNA template. 3) Cooperative stapling of unprotected peptides at lysine and tyrosine or arginine with simple formaldehyde.      

  1. A General Strategy for Synthesis of Cyclophane-Braced Peptide Macrocycles via Palladium-Catalyzed Intramolecular sp3 C−H Arylation. Xuekai Zhang, Gang Lu, Meng Sun, Madhu Mahankali, Yanfei Ma, Mingming Zhang, Wangde Hua, Yuting Hu, Qingbing Wang, Jinghuo Chen, Gang He*, Xiangbing Qi*, Weijun Shen*, Peng Liu* and Gong Chen*. Nature Chem. 2018, 10, 543.
  2. Construction of Natural-Product-Like Cyclophane-Braced Peptide Macrocycles via sp3 C−H Arylation. Bo Li, Xinghua Li, Boyang Han, Zhijie Chen, Xuekai Zhang, Gang He, and Gong Chen*. J. Am. Chem. Soc. 2019, 141, 9401-9407.
  3. Streamlined Construction of Peptide Macrocycles via Palladium-catalyzed Intramolecular S-Arylation in Solution and on DNA. Peng Yang, Xuan Wang, Bo Li, Yixuan Yang, Jingfeng Yue, Yanrui Suo, Huarong Tong, Gang He, Xiaojie Lu*, and Gong Chen*. Chem. Sci. 2021, 12, 5804-5810.
  4. Cooperative Stapling of Native Peptides at Lysine and Tyrosine or Arginine with Formaldehyde. Bo Li, Hong Tang, Aneta Turlik, Zhao Wan, Xiao-Song Xue, Li Li, Xiaoxiao Yang, Jiuyuan Li, Gang He， K.N. Houk*, and Gong Chen* Angew. Chem., Int. Ed. 2021, 60, 6646-6652.