Polysaccharides are complex carbs made of glucose units linked by glycosidic bonds. They come in different forms like cellulose, starch, and glycogen, each with unique structures and functions in nature.

Glycal assembly is a clever way to build polysaccharides in the lab. It uses special sugar building blocks and controlled reactions to make complex carbohydrates, mimicking how our bodies naturally create these important molecules.

Polysaccharide Structure and Composition

Structure of cellulose and starch

• Polysaccharides composed of glucose monomers linked by glycosidic bonds
  • Glycosidic bonds form between the anomeric carbon (C1) of one glucose and a hydroxyl group of another glucose (sucrose, lactose)
• Cellulose linear polymer with β(1→4) glycosidic bonds
  • Hydroxyl groups oriented equatorially allow extensive hydrogen bonding between chains resulting in a rigid, fibrous structure (cotton, wood)
• Starch composed of amylose and amylopectin
  • Amylose linear polymer with α(1→4) glycosidic bonds and axially oriented hydroxyl groups forming a helical structure
  • Amylopectin branched polymer with α(1→4) and α(1→6) glycosidic bonds creating branch points every 24-30 glucose units (potatoes, rice)

Glycogen as energy storage

• Primary energy storage polysaccharide in animals stored in the liver and skeletal muscle
• Similar to amylopectin with α(1→4) and α(1→6) glycosidic bonds but more highly branched with branch points every 8-12 glucose units
• Compact, spherical structure due to extensive branching unlike starch's helical amylose
• Glucose monomers rapidly released by glycogen phosphorylase and debranching enzymes for energy production or conversion to glucose-6-phosphate for metabolic pathways

Glycal assembly for polysaccharides

• Strategy using glycal building blocks, unsaturated sugars with a double bond between C1 and C2, prepared from glycosyl halides or hemiacetals
• Protection steps involve protecting hydroxyl groups not involved in glycosidic bond formation as esters (acetates) or ethers (benzyl ethers) based on stability and ease of removal
• Coupling reactions in a two-step process:
  1. Epoxidation of the glycal double bond using dimethyldioxirane (DMDO) to form a 1,2-anhydrosugar
  2. Nucleophilic attack by a free hydroxyl group of another glycal on the anomeric carbon (C1) of the 1,2-anhydrosugar, forming a glycosidic bond with controlled stereochemistry
• Deprotection removes protecting groups using appropriate conditions like base-catalyzed ester hydrolysis or hydrogenolysis of benzyl ethers
• Advantages include stereoselective synthesis of complex polysaccharides using a modular approach with common building blocks and coupling reactions, enabling synthesis of branched and linear polysaccharides
• Glycosyltransferases are enzymes that catalyze the formation of glycosidic bonds in biological systems

Carbohydrate Diversity and Glycobiology

• Monosaccharides are the simplest carbohydrate units and serve as building blocks for more complex structures
• Oligosaccharides are short chains of monosaccharides, typically containing 2-10 sugar units
• Glycobiology is the study of the structure, biosynthesis, and biology of saccharides in living organisms