Cysteine Catalyzed Pictet-Spengler Reaction: a Convenient and Mild Method for Synthesis of Spiroindolones

• Published in: Catalysis letters Vol. 154; no. 8; pp. 4586 - 4593
• Main Authors: Zhao, Xiao-Ting, Li, Wen-Dian, Tao, Fei-Yan, Wang, Na
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2024
• Subjects: Catalysis; Chemistry; Chemistry and Materials Science; Industrial Chemistry/Chemical Engineering; Organometallic Chemistry; Physical Chemistry; Spiroindolones; Cysteine; Catalysis; Pictet-Spengler reaction
• ISSN: 1011-372X; 1572-879X
• DOI: 10.1007/s10562-024-04698-8

Pictet-Spengler reaction is one of the main ways to synthesize spiroindolones, which widely exists in natural products and pharmaceutical agents. We accidentally discovered bovine serum albumin (BSA) had catalytic activity for Pictet-Spengler reaction previously. After a series of exploratory experiments around the catalytic process, it was found that some amino acids played a key role. It is worth noting that, Pictet-Spengler reaction catalyzed by amino acids has been rarely described. Herein, we report the cysteine-catalyzed Pictet-Spengler reaction between tryptamine and isatin under metal-free and convenient conditions. The catalytic performance of amino acid was optimized through screening reaction conditions such as time, temperature, solvent, molar ratio and catalyst amount and a series of spiroindolones can be obtained in moderate to excellent yields. The present investigation featured relatively mild reaction conditions with good functional group tolerance and provided an alternative method for preparation of spiroindolones. Graphical Abstract