Alkynylamide condensation reagents (Figure 1) are a type of reagent with a new structure developed by Professor Zhao Junfeng's research group and are used for the direct condensation of acids and amines. They are characterized by moderate activity and can effectively avoid the activation of the α-position chiral center of carboxylic acid with the amide. Racemization issues during bond formation. In addition, they have small molecular weight (MYTsA 209; MYMsA 133), good atom economy, and can be efficiently prepared through a one-step reaction under mild conditions [1].

Application

Alkynylamide condensation reagents are widely used (Figure 2):

Figure 1 Alkynylamide condensation reagents

1. Ordinary amide condensation.

2. Formation of peptide bonds such as peptide synthesis, peptide fragment connection, and cyclic peptide synthesis: moderate activity, reaction under neutral conditions, completely avoiding the risk of alkali-induced racemization in ordinary peptide synthesis; simple operation, no need for additional reagents and catalysts [ 1].

3. Macrolactonization reaction: Especially in the macrolactonization reaction of open-chain hydroxy acids containing α-chiral centers or α, β-unsaturated open-chain hydroxy acids containing conjugated olefins, it can be avoided Problems such as racemization of the α-chiral center and Z/E isomerization of the C2-C3 double bond caused by traditional macrolide reagents [2].

4. Promote the direct condensation of carboxylic acid with alcohol/phenol and thiol/thiophenol, and be used in the synthesis of esters, thioesters, thiocarbonyl esters, and disulfide esters [3].

5. Synthesis of thioamide and thiopeptides: The thioacylation reagent developed based on acetylenic amide condensation reagents can be used for the synthesis of thioamide, and the thioacylation reagent derived from amino acids can be used in the liquid phase and solid phase synthesis of peptides. Precisely introduce thioamide bonds into the polypeptide main chain skeleton in a modular manner to solve the bottleneck problem of difficult construction and easy racemization of thioamide-substituted peptides [4-5].

Figure 2 Alkynylamide condensation reagents can be used for the synthesis of amides, polypeptides, cyclic peptides, thiopeptide esterification, thioesters, and macrolides

J&K Scientific provides acetylenic amide condensation reagents developed by Professor Zhao Junfeng:

Professor Zhao Junfeng is a distinguished professor and doctoral supervisor at Jiangxi Normal University. The research direction is the chemical synthesis and modification of polypeptides and proteins; the efficient synthesis of complex polycyclic molecules. He has published more than 40 papers as the first author or corresponding contact in internationally renowned magazines such as J. Am. Chem. Soc., Angew. Chem. Int. Ed. Hosted one major research plan of the National Natural Science Foundation of China, one general project and one regional project, one major project of the Jiangxi Provincial Department of Science and Technology, and one key project of the Jiangxi Provincial Department of Education. He has won honors such as the 7th Overseas Chinese Contribution Award of the All-China Federation of Returned Overseas Chinese and the 2019 "The Chemical Society of Japan Lectureship Award" Core Lecture Award.

References

Long Hu, Silin Xu, Zhenguang Zhao, Yang Yang, Zhiyuan Peng, Ming Yang, Changliu Wang, Junfeng Zhao. J. Am. Chem. Soc. 2016, 138, 13135-13138.
Ming Yang, Xuewei Wang, Junfeng Zhao. ACS Catal. 2020, 10, 5230-5235.
Xuewei Wang, Yang Yang, Yongli Zhao, Sheng Wang, Wenchang Hu, Jinmei Li, Zihao Wang, Fengling Yang, and Junfeng Zhao. J. Org. Chem. 2020, 85, 6188-6194.
Jinhua Yang, Changliu Wang, Silin Xu, Junfeng Zhao. Angew. Chem. Int. Ed. 2019, 58, 1382-1386.
Jinhua Yang, Changliu Wang, Chaochao Yao, Chunqiu Chen, Yafang Hu, Guifeng He, and Junfeng Zhao. J. Org. Chem. 2020, 85, 1484-1494.