Metal-free quinolylation of the primary amino groups of amino acid derivatives and peptides with dihydrooxazolo[3,2-]quinoliniums

• Published in: Green chemistry : an international journal and green chemistry resource : GC Vol. 21; no. 15; pp. 4231 - 4237
• Main Authors: Liu, Peng, Li, Bo, Xi, Mengyu, Chen, Zhaoqiang, Sun, Haiguo, Huan, Xiajuan, Xu, Xuejun, Zhang, Yong, Zou, Kun, Jiang, Xiangrui, Miao, Zehong, Liu, Jinggen, Shen, Jingshan, Chen, Kaixian, Zhu, Weiliang
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 2019; Royal Society of Chemistry
• Subjects: Acids; Amino acids; Amino groups; Biological activity; Biology; Butanol; Chemical modification; Chemical reactions; Chemistry; Chemistry, Multidisciplinary; Cyano groups; Derivatives; Green & Sustainable Science & Technology; Green chemistry; Metals; Organic chemistry; Peptides; Pharmaceutical industry; Phenolic compounds; Phenols; Physical Sciences; Science & Technology; Science & Technology - Other Topics; THERAPEUTICS; TERMINAL PROTEIN MODIFICATION; TYROSERLEUTIDE; OXYTOCIN; OPTIMIZATION; FUTURE; DISCOVERY
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/c9gc01442j

The chemical modification of the primary amino groups of amino acid derivatives and peptides is an important process in the pharmaceutical industry and the field of chemical biology. However, suitable reactions that can be carried out under mild and environmentally friendly conditions are limited. We present a versatile method to selectively modify primary amino groups using novel dihydrooxazolo[3,2- a ]quinoliniums in 1-butanol as solvent under mild and metal-free conditions. The application of this method to peptides with primary amino, secondary amino, amide, alcoholic hydroxyl, phenolic hydroxyl, disulfide bond, ester and cyano groups revealed that only the primary amino groups were selectively modified, suggesting that this method is compatible with other reactive moieties. We also demonstrated that the quinolylation of existing peptides affected peptide bioactivity and stability, indicating that the novel dihydrooxazolo[3,2- a ]quinoliniums can be widely applied, especially in medicinal chemistry and chemical biology. A new metal-free method for the N -quinolylation of primary amino groups using novel dihydrooxazolo[3,2- a ]quinoliniums showing good compatibility with other reactive moieties.