Why is the anomeric carbon OH always the nucleophile in disaccharaide glycosidic linakages?

[manohman]

When you make a disaccharaide, its the anomeric carbon OH that is the nucleophile and the other sugar's OH that is the leaving group

(so like with a 1'4 sugar. its the carbon 4's OH, that leaves and the anomeric carbon's OH that makes the bond).

Yet when you combine glucose with an alcohol to form a glycosidic linkage, the anomeric carbon OH is now the leaving group and the alcohol the nucleophile.

[http://www.chem.ualberta.ca/~vederas/Chem_164/images/Resource Folder/glc_acetal.gif
](http://www.chem.ualberta.ca/~vederas/Chem_164/images/Resource Folder/glc_acetal.gif)

The reasoning for the latter is that the anomeric OH leaves because the carbocation that results has resonance with the O in the ring. So that carbocation is more stable than any other carbocation that might form if any OH leaves. So the anomeric OH leaves preferentially/more often.


That's why when you combine an alcohol with a glucose, only the anomeric carbon becomes a carbocation and gets attatcked by the alcohol to become an acetal.


Yet with disaccharaides, the anomeric carbon OH doesn't leave anymore but instead serves as the nucleophile.

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[BerkReviewTeach]

What I would suggest you do to wrap your head around this is first consider simple substitution reactions like the SN1 and SN2. Which one undergoes inversion of chirality, the nucleophile or the electrophile? It is the electrophile that undergoes inversion. Now look at C4 and C1 of the glycosidic linkage of whatever disaccharide you were considering in your example above. Which one underwent a change in chirality? C4 does not change while the anemic carbon can be either alpha or beta, which implies that the anomeric carbon must have been the electrophilic site and the C4 hydroxyl must have acted as the nucleophile. While the mechanism is not a simple SN1 or SN2, you have a similar result in terms of stereochemistry.

So how are you reaching your conclusion that the anomeric hydroxyl is nucleophile and C4 is electrophilic? Where are you getting this from? The picture you posted shows the anomeric hydroxyl leaving to form an sp2-intermediate, which then gets attacked by an ROH nucleophile. It does not show a sugar attacking the anomeric carbon, but we can assume that the ROH represents the OH on C4 in your example.