Cobalt's dual role in promoting C3-glycosylation of indoles: unraveling mechanistic insights

• Main Authors: Mu, Qiu-Qi, Guo, Aoxin, Cai, Xin, Qin, Yang-Yang, Liu, Xing-Le, Ye, Fang-Zhen, Yang, Hui-Jie, Xiao, Xiong, Liu, Xue-Wei
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2024
• Subjects: Chemistry; C3-Glycosylation; Indoles
• Online Access: https://hdl.handle.net/10356/173474
• Institution: Nanyang Technological University

In this study, we present a cobalt-catalyzed C3-glycosylation of indoles using unfunctionalized glycals, yielding 3-indolyl-C-deoxyglycosides. These compounds hold promise as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for treating type 2 diabetes. Control experiments unveiled that cobalt assumes a dual role, facilitating catalytic C-glycosylation while unexpectedly driving the anomerization of α-anomers through endocyclic cleavage of the C1-O5 bond, resulting in the formation of β-C-deoxyglycosides. Furthermore, density functional theory (DFT) calculations shed light on the reaction mechanism, emphasizing the significant role of the pyridine group of indole in stabilizing transition states and intermediates.