Macrocyclization of bioactive peptides with internal thiazole motifs via palladium-catalyzed C–H olefination
2022
Cai, Chuangxu | Wang, Feifei | Xiao, Xiuyun | Sheng, Wangjian | Liu, Shu | Chen, Jun | Zheng, Jie | Xie, Ran | Bai, Zengbing | Wang, Huan
Peptides containing thiazole fragments represent a large group of bioactive compounds with potential medicinal applications. However, methods for efficient synthesis of these compounds with structural diversity are limited. Herein, we report a method for modification and macrocyclization of thiazole-containing peptides through palladium-catalyzed δ-C(sp²)–H olefination. In this protocol, the thiazole and neighboring amide bonds act as directing groups, which allows site-specific olefination of phenylalanine, tryptophan and tyrosine residues. This chemistry exhibits broad substrate scope and provides facile access to peptide-peptide conjugates and peptide macrocycles. Our results highlight the potency and applicability of thiazole motifs in promoting Pd-catalyzed functionalization of peptides.
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