Zinc(II) Iodide-Directed β-Mannosylation: Reaction Selectivity, Mode, and Application.

Area of Science:

• Carbohydrate Chemistry
• Organic Synthesis
• Glycobiology

Background:

• Stereoselective synthesis of 1,2-cis-glycosidic bonds, particularly β-mannosides, is a significant challenge in carbohydrate chemistry.
• Existing glycosylation methods often lack efficiency and versatility for complex oligosaccharide construction.

Purpose of the Study:

• To develop a direct, efficient, and versatile glycosylation methodology for the systematic synthesis of oligosaccharides and glycoconjugates.
• To achieve highly stereoselective construction of 1,2-cis-β-mannosidic linkages.

Main Methods:

• Utilized a zinc iodide (ZnI2)-mediated direct mannosylation strategy.
• Employed easily accessible 4,6-O-tethered mannosyl trichloroacetimidate donors.
• Applied density functional theory (DFT) calculations to investigate reaction mechanisms.

Main Results:

• Achieved highly stereoselective construction of 1,2-cis-β-mannosidic linkages.
• Demonstrated versatility by successful β-mannosylation of diverse alcohol acceptors including natural products and amino acids.
• Enabled modular synthesis of a key trisaccharide intermediate for N-glycan synthesis through iterative mannosylation and deprotection.

Conclusions:

• The developed ZnI2-mediated mannosylation strategy offers a streamlined and effective approach for synthesizing complex carbohydrates.
• The methodology facilitates the modular construction of oligosaccharides and glycoconjugates, including N-glycan precursors.
• Mechanistic studies revealed the crucial roles of zinc cations in donor activation and stereochemical control.