Ferrier/Aza-Wacker/Epoxidation/Glycosylation (FAWEG) Sequence to Access 1,2-Trans 3-Amino-3-deoxyglycosides

3-Amino-3-deoxyglycosides constitute an essential class of nitrogen-containing sugars. Among them, many important 3-amino-3-deoxyglycosides possess a 1,2-trans relationship. In view of their numerous biological applications, the synthesis of 3-amino-3-deoxyglycosyl donors giving rise to a 1,2-trans glycosidic linkage is thus an important challenge. Even though glycals are highly polyvalent donors, the synthesis and reactivity of 3-amino-3-deoxyglycals have been little studied. In this work, we describe a new sequence, involving a Ferrier rearrangement and subsequent aza-Wacker cyclization that allows the rapid synthesis of orthogonally protected 3-amino-3-deoxyglycals. Finally a 3-amino-3-deoxygalactal derivative was submitted for the first time to an epoxidation/glycosylation with high yield and great diastereoselectivity, highlighting FAWEG (Ferrier/Aza-Wacker/Epoxidation/Glycosylation) as a new approach to access 1,2-trans 3-amino-3-deoxyglycosides.

Automated summary

3-Amino-3-deoxyglycosides are important nitrogen-containing sugars, with many important ones having a 1,2-trans configuration. The synthesis of 3-amino-3-deoxyglycosyl donors that can form a 1,2-trans glycosidic linkage is a significant challenge due to their biological applications. This work presents a new sequence involving Ferrier rearrangement and subsequent aza-Wacker cyclization for the rapid synthesis of orthogonally protected 3-amino-3-deoxyglycals. Additionally, the epoxidation/glycosylation of a 3-amino-3-deoxygalactal derivative was successfully achieved with high yield and diastereoselectivity, demonstrating FAWEG as a new approach for accessing 1,2-trans 3-amino-3-deoxyglycosides.