General Method for the Synthesis of α- or β-Deoxyaminoglycosides Bearing Basic Nitrogen

Area of Science:

• Organic Chemistry
• Carbohydrate Chemistry
• Synthetic Methodology

Background:

• Conventional methods for synthesizing nitrogen-containing glycosides are hindered by Lewis acid promoter coordination issues.
• Aminoglycosides often yield diastereomeric mixtures due to the absence of a C2 substituent.
• A need exists for a general and stereoselective method to synthesize O-glycosides with basic nitrogen moieties.

Purpose of the Study:

• To develop a novel synthetic strategy for accessing α- or β- 2,3,6-trideoxy-3-amino- and 2,4,6-trideoxy-4-amino O-glycosides.
• To apply this method to the synthesis of various important amino sugar derivatives, including forosamine, pyrrolosamine, acosamine, and ristosamine.
• To investigate the stereochemical outcomes influenced by the substituent orientation at low temperatures.

Main Methods:

• Reductive lithiation of thiophenyl glycoside donors.
• Trapping of the generated anomeric anions with 2-methyltetrahydropyranyl peroxides.
• Utilizing primary and secondary peroxides as electrophiles for diverse amino sugar synthesis.

Main Results:

• Successful synthesis of α-linked amino glycosides in 60-96% yield with >50:1 selectivity.
• Synthesis of β-linked amino glycosides achieved in 45-94% yield with 1.7->50:1 stereoselectivity.
• Axial amine substituents favored β-product formation at low temperatures, contrasting with equatorial substituents.

Conclusions:

• A general and efficient strategy for synthesizing O-glycosides bearing basic nitrogen has been established.
• The method provides high yields and excellent stereoselectivity for both α- and β-linked amino sugars.
• This approach offers a valuable tool for accessing complex amino sugar derivatives relevant in medicinal chemistry and glycobiology.