Glucose: ring closure and glycosides template

Open-chain D-glucose closes to β-D-glucopyranose; with methanol and HCl the anomeric OH is lost as water to an oxocarbenium ion, which methanol traps to give the methyl glucopyranosides (mainly α at equilibrium; the β anomer is drawn).

Mechanism step by step

The C5 hydroxyl adds to the aldehyde (a cyclic hemiacetal); acid and methanol then give a glycoside

1. Ring closure – The C5–OH attacks the aldehyde carbon
2. Proton transfer – β-D-Glucopyranose, a cyclic hemiacetal (via the solvent)
3. Protonation – Acid protonates the anomeric OH
4. Oxocarbenium ion – The ring O pushes out water
5. Methanol adds – From either face: α and β glycosides form (α predominates)
6. Deprotonation – Methyl β-D-glucopyranoside

Key points

• Ring closure makes C1 a new stereocentre: α (OH axial, 36%) and β (OH equatorial, 64%) interconvert in water (mutarotation).
• The cyclic hemiacetal opens easily, so glucose is a reducing sugar (positive Tollens’ and Fehling’s tests).
• A glycoside is an acetal: stable in base, not reducing, hydrolysed by aqueous acid or enzymes.
• Glycosidic bonds join sugars in maltose, sucrose, starch and cellulose; in cells enzymes make them from activated sugars (UDP-glucose).

Drawn with 196 atoms, 20 arrows, 11 shapes – every one editable in MolDraw.

Sources

• Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012, ch. 42 Textbook
• Nelson & Cox, Lehninger Principles of Biochemistry, 8th ed., 2021, ch. 7 Textbook