Glycoside - Online Tutor, Practice Problems & Exam Prep

O-glycosidation is a crucial reaction of monosaccharides, where they react at the anomeric carbon in acidic conditions to form O-glycosides, a type of acetal. This process, similar to Fischer esterification, involves protonation of the hydroxyl group, leading to the formation of an oxocarbenium cation, which is resonance stabilized. The reaction selectively adds an alkyl group to the anomeric position, resulting in a mixture of alpha and beta anomers due to mutarotation. Understanding this mechanism is essential for grasping carbohydrate chemistry.

General Reaction

In this video, I want to teach you guys the most important reaction of monosaccharides, and that is called O-glycosidation. Alright, guys, so as you might or may not know, monosaccharides have the ability to react at the oxygen position in several different ways. Okay? But in acidic conditions, monosaccharides can alkylate selectively at the anomeric position to produce what we call O-glycosides. That means this type of bond here, it's an acetal where you have an R group specifically attached only to the oxygen position that's called a glycoside. It gets an "-oside" ending. Okay. This process is also known as Fischer glycosidation and it actually has a lot of similarities to another reaction that you might have learned with Fischer's name on it, Fischer esterification. You guys remember that? It's very similar because it proceeds through a reversible intermediate and it's acid catalyzed. There are oxygen and carbons involved, it's not a very wild mechanism. So once you get it, it's going to be pretty easy okay?

Now let me show you guys the general structure of the general formula here. The general reaction is you take a beta-D-glucopyranose and you react it with alcohol and acid. So when I said it's similar to Fischer esterification it's because that's the same thing that you would have used for a carboxylic acid, right? It's the same Fischer esterification, you would get an ester, right? You would get OR. Well, it's the same thing that happens here except that it specifically only happens to this O, and it turns that O into an OR group that has the same R group here, but it's also since it's only at the anomeric carbon, you're going to get a mixture of anomers obviously due to mutarotation. So you're going to get some kind of combination of alpha and beta anomers depending on the specific monosaccharide and which one is preferred for that setting, okay? At the end, what we get is a new functional group called an acetal because you have OR groups coming off of both positions, OROR. And if it's an acetal that specifically once again gets the name of O-glycoside because it specifically has an R group at the anomeric position. Okay?

So you might be saying okay Johnny, I'm getting what you're saying, but how can you guarantee that it's only going to happen at the anomeric carbon? Why doesn't it happen here or here or here? Well, guys, the reason is going to lie in this intermediate called an oxocarbenium intermediate, which is a very special intermediate. It's the important intermediate of this reaction and that's what I'm going to show you in the next video. In the next video, I'm going to prove to you guys how this can only happen at the anomeric position and it can't happen anywhere else. So let's go ahead and go to the mechanism.

Here’s what students ask on this topic:

What is O-glycosidation in monosaccharides?

O-glycosidation is a reaction where monosaccharides react at the anomeric carbon in acidic conditions to form O-glycosides, a type of acetal. This process involves protonation of the hydroxyl group at the anomeric position, leading to the formation of an oxocarbenium cation, which is resonance stabilized. The reaction selectively adds an alkyl group to the anomeric position, resulting in a mixture of alpha and beta anomers due to mutarotation. This mechanism is crucial for understanding carbohydrate chemistry.

How does the mechanism of O-glycosidation work?

The mechanism of O-glycosidation starts with the protonation of the hydroxyl group at the anomeric carbon, creating a good leaving group. This leads to the formation of an oxocarbenium cation, which is resonance stabilized. The cation is then attacked by an alcohol (ROH), adding an alkyl group to the anomeric position. The final step involves deprotonation to form the O-glycoside. This reaction is selective for the anomeric carbon due to the formation of the resonance-stabilized oxocarbenium intermediate.

What is the role of the oxocarbenium cation in O-glycosidation?

The oxocarbenium cation plays a crucial role in O-glycosidation by stabilizing the intermediate formed during the reaction. This cation is resonance stabilized, which makes it a favorable intermediate. The formation of this cation ensures that the reaction occurs specifically at the anomeric carbon, as no other position in the monosaccharide can form such a stabilized intermediate. This selectivity is key to the formation of O-glycosides.

Why does O-glycosidation only occur at the anomeric carbon?

O-glycosidation occurs exclusively at the anomeric carbon because this is the only position that can form a resonance-stabilized oxocarbenium cation. The anomeric carbon is adjacent to an oxygen atom, allowing the formation of a double bond and the stabilization of the positive charge through resonance. Other positions in the monosaccharide do not have this capability, making the anomeric carbon the unique site for this reaction.

What is the difference between Fischer esterification and Fischer glycosidation?

Fischer esterification and Fischer glycosidation are similar in that both are acid-catalyzed reactions involving the formation of esters and acetals, respectively. In Fischer esterification, a carboxylic acid reacts with an alcohol to form an ester. In Fischer glycosidation, a monosaccharide reacts with an alcohol at the anomeric carbon to form an O-glycoside. Both processes involve protonation, formation of a resonance-stabilized intermediate, and subsequent nucleophilic attack by the alcohol.