Ynamide-Mediated Thioamide and Primary Thioamide Syntheses
Changliu Wang, Chunyu Han, Jinhua Yang*, Zhenjia Zhang, Yongli Zhao and Junfeng Zhao*
*College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China,
Email: zhaojf
gzhmu.edu.cn
C. Wang, C. Han, J. Yan, Z. Zhang, Y. Zhao, J. Zhao, J. Org. Chem., 2022, 87, 5620-5629.
DOI: 10.1021/acs.joc.1c03076
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Abstract
An environmentally friendly ynamide-mediated thioamidation of monothiocarboxylic acids with amines or ammonium hydroxide provides thioamides and primary thioamides and tolerates a wide variety of functional groups. The stereochemical integrity of α-chiral monothiocarboxylic acids was maintained during the activation step and subsequent aminolysis process.
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Details
The article discusses an environmentally friendly method for synthesizing thioamides and primary thioamides using ynamides. This method involves the reaction of monothiocarboxylic acids with amines or ammonium hydroxide under mild conditions, utilizing NaSH as the sulfur source. This approach avoids the use of toxic and malodorous organic sulfur reagents, making it practical and eco-friendly. The reaction conditions are simple and can tolerate various functional groups, maintaining the stereochemical integrity of α-chiral monothiocarboxylic acids, thus preventing racemization. The method has been successfully applied to synthesize thioamide-modified drugs and primary thioamides, which can be further transformed into thiazolyl-modified peptides. The study highlights the broad substrate scope and high yields of the desired products, demonstrating the method's potential in organic synthesis and medicinal chemistry. The article also provides detailed experimental procedures and characterizations of the synthesized compounds, emphasizing the method's efficiency and applicability in modifying peptide C-termini and preparing thioamide-substituted pharmaceuticals.
Ynamide-Mediated Thionoester and Dithioester Syntheses
C. Yao, J. Yang, X. Lu, S. Zhang, J. Zhao, Org. Lett., 2020, 22, 6628-6631.
Key Words
ID: J42-Y2022
