Establishment of Guidelines for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of Reactivity

• Published in: Angewandte Chemie 2019-11, Vol.131 (47), p.16931-16935
• Main Authors: Chang, Chun‐Wei, Wu, Chia‐Hui, Lin, Mei‐Huei, Liao, Pin‐Hsuan, Chang, Chun‐Chi, Chuang, Hsiao‐Han, Lin, Su‐Ching, Lam, Sarah, Verma, Ved Prakash, Hsu, Chao‐Ping, Wang, Cheng‐Chung
• Format: Article
• Language: English
• Subjects: Chemical reactions; Chemistry; Diastereoselektivität; Glycosylation; Glykosylierung; Guidelines; Halides; Intermediates; Kohlenhydrate; Organic chemistry; Selectivity
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201906297

Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates: glycosyl triflates and glycosyl halides from N‐halosuccinimide (NXS)/TfOH. The formation of glycosyl halide is highly correlated with the production of α‐glycoside. These findings enable glycosylation reactions to be foreseen by using RRVs as an α/β‐selectivity indicator and guidelines and rules to be developed for stereocontrolled glycosylation. Selektivitäts‐Tachometer: Der relative Reaktivitätswert (RRV) von Thioglykosiden ist ein geeigneter Indikator, um die Stereoselektivitäten chemischer Glykosylierungen anzuzeigen.