Expanding 1‐Aminosugar Synthesis through Activated Glycals’ Reactivity

• Published in: European journal of organic chemistry 2024-11, Vol.27 (41), p.n/a
• Main Authors: Li, Linlin, Lemouton, Emma, Al Ayi, Yahya, Ryzhakov, Dmytro, Retailleau, Pascal, Messaoudi, Samir, Ferry, Angélique
• Format: Article
• Language: English
• Subjects: 1-aminoglycoside; Amines; Aminoglycosides; ferrier-type reactivity; glycal; Nucleophiles
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202400728

Glycal family offers an interesting platform whose reactivity let the possibility to reach diverse glycoanalogues. In particular, the Ferrier rearrangement allows the introduction of diverse nucleophiles on the anomeric position but stays limited with regard to the nitrogen‐containing nucleophiles, which can be possibly used with success. Herein, we utilize peracetylated C2‐substituted glycal substrates to achieve Ferrier‐type 1‐aminoglycoside compounds under activator‐free conditions, resulting in moderate to good yields and good to excellent β‐selectivity. Various secondary amines have been successfully employed. We explored the influence of C2‐substitution (electron‐withdrawing character) and glycal configuration, synthesizing 20 different 1‐aminoglycosides through this method. A simple and efficient protocol for the synthesis of 1‐aminosugars under mild reaction conditions has been developed. This method utilizes activated glycals as substrates and successfully achieves the Ferrier‐type reaction in the presence of various alkyl amines to lead to 1‐aminoglycosides in good yields and good to excellent β‐selectivity.