Synthesis and structure of d-glucuronolactone derived carboxamides

Area of Science:

• Carbohydrate Chemistry
• Organic Synthesis
• Structural Chemistry

Background:

• Glucuronic acid derivatives are important in biological systems.
• Efficient synthesis of functionalized glucuronamides is challenging.
• Selective protection and deprotection strategies are crucial for carbohydrate modification.

Purpose of the Study:

• To synthesize novel furano-glucuronamides from protected D-glucurono-6,3-lactone furanosides.
• To explore different protection and deprotection strategies for selective functionalization.
• To establish a reliable method for obtaining fully protection-differentiated glucofuranamides.

Main Methods:

• Treatment of 5-O-protected and 1,2-acetonide-protected D-glucurono-6,3-lactone furanosides with ammonia.
• Investigating various O3 protecting groups and O5-deprotection routes.
• Utilizing X-ray crystallography to determine the structure of key intermediates and products.

Main Results:

• Successful conversion of protected lactones to furano-glucuronamides.
• Demonstration that O3-benzylation of O5-TDBMS protected intermediates leads to undesired side reactions like silyl migration and lactone reclosure.
• Identification of 5-O-PMB protection as the optimal strategy for selective synthesis of glucofuranamides.
• X-ray crystal structures of a protected glucurono-6,3-lactone and a glucuronamide derivative were obtained.

Conclusions:

• A novel route to furano-glucuronamides has been developed.
• The choice of protecting group significantly impacts the success of the synthesis.
• 5-O-PMB protection offers a reliable method for synthesizing fully protection-differentiated glucofuranamides.
• Structural elucidation by X-ray crystallography confirms the synthetic outcomes.