Glycosylamine isomerization
Amadori rearrangement
How the Amadori rearrangement works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Reducing aldose + primary amine (lysine ε-NH₂). Conditions: Mild acid or base, pH 4–7, 25–100 °C. Bonds formed: C=N (glycosylamine); C=O at C2 (ketose); C–N; bonds broken: C=O (aldehyde); α C–H at C2. Stereochemistry: C2 stereocenter destroyed; C1 becomes CH₂. Rate and selectivity: Enolization of the iminium is rate-limiting.
At a glance
Step 1: Aldose + amine → imine
A reducing sugar's open-chain aldehyde condenses with an amine (often a protein's lysine side chain) to form a glycosylamine — ordinary imine-forming Schiff-base chemistry, applied here to a sugar.
Step 2: Enolization to the enaminol
Acid or base catalyzes tautomerization of this glycosylamine through an iminium/enaminol intermediate — mechanistically the same enolization used throughout carbonyl chemistry, just shuttling the double bond from the ring-opened imine to an adjacent carbon.
Step 3: Tautomerize to the ketosamine
The product is a 1-amino-1-deoxy-ketose — a stable, rearranged sugar-amine adduct that resists simple hydrolysis back to the starting materials, and is the key early intermediate in the Maillard browning reaction.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- Lys
- Lysine. Basic amino acid with a nucleophilic –NH₂.
How it compares with related reactions
| Amadori rearrangement | Acetic acid transfers a proton to water | Acid-catalyzed amide hydrolysis | |
|---|---|---|---|
| Reagents | Reducing aldose + primary amine (lysine ε-NH₂) | Acetic acid (pKa 4.76) + water | Amide, H₃O⁺ (HCl or H₂SO₄), H₂O |
| Conditions | Mild acid or base, pH 4–7, 25–100 °C | Aqueous solution, 25 °C | 6 M acid, reflux (hours) |
| Stereochemistry | C2 stereocenter destroyed; C1 becomes CH₂ | None (achiral species) | No stereocentre created; α-stereocentres retained |
| Rate / selectivity | Enolization of the iminium is rate-limiting | Equilibrium: Ka = 1.8 × 10⁻⁵, lies mostly left | Water attack / C–N cleavage rate-limiting; far slower than ester hydrolysis |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Amadori rearrangement?
Reducing aldose + primary amine (lysine ε-NH₂). Conditions: Mild acid or base, pH 4–7, 25–100 °C.
Which bonds are formed and which are broken?
Formed: C=N (glycosylamine); C=O at C2 (ketose); C–N. Broken: C=O (aldehyde); α C–H at C2.
What is the stereochemical outcome?
C2 stereocenter destroyed; C1 becomes CH₂
What controls the rate or the selectivity?
Enolization of the iminium is rate-limiting
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go