Monosaccharides - Cyclization: Videos & Practice Problems

Monosaccharides primarily exist in cyclic forms, specifically as furanose (5-membered) and pyranose (6-membered) rings. Cyclization occurs through nucleophilic addition of the penultimate alcohol to the electrophilic carbonyl, resulting in two anomers: alpha and beta. The alpha anomer has the hydroxyl group trans to the C5 carbon, while the beta anomer has it cis. The predominance of the beta anomer in glucose is due to equatorial preference. Understanding these structures is crucial for grasping carbohydrate chemistry and the concept of mutarotation, where anomers interconvert through the straight chain form.

Monosaccharides - Cyclization

Now it's time to dive deep on the most important reaction of monosaccharides, and that is cyclization. So guys, it turns out that in aqueous solutions, monosaccharides are most stable in their cyclic form. Monosaccharides can form stable 5 and 6 membered rings, which have different names. A 5-carbon cyclic sugar is going to be called a furanose, and a 6-carbon cyclic sugar is going to be called a pyranose. There are no 4-carbon cyclic sugars or 7 and greater because those aren't stable as rings anymore. So, really the only stable ones that you have to worry about are furanose and pyranose. Cool? The nucleophilic addition of the penultimate alcohol to the electrophilic carbonyl leads to cyclization. It doesn't always have to be the penultimate alcohol, but usually, it is. Let me just kind of show you guys what we're talking about here. This is D-glucose, as you guys should be well aware of. Here is the penultimate alcohol and the electrophilic carbon. Remember, it has a partial positive charge. The nucleophilic addition, meaning the O comes in, attacks, and kicks electrons up to the O; that reaction right there is going to cyclize this straight chain glucose into one of 2 possible rings.

Now, why would you get 2 possible rings? Well, the carbonyl carbon, if you think about the geometry of a double bond of an sp2 hybridized carbon, it's trigonal planar. That means that it can be attacked either from the top or from the bottom. The oxygen could either come around the top and attack or around the bottom and attack. It turns out that this is going to set up for stereoisomers that are possible. When these monosaccharides cyclize, 2 different C1 epimers are possible. The way that monosaccharides are numbered is always from the one carbon being the point of attack being the carbonyl because that's the top carbon. This is C2, C3, C4, C5, and C6. After cyclization, this becomes carbon 1, carbon 2, carbon 3, carbon 4, carbon 5, and this is actually carbon 6 right here. The oxygen doesn't get a number because it's not a carbon. When I say that cyclization leads to 2 different C1 epimers, what I'm saying is that you're going to have 2 different chiralities at carbon 1 that are possible, and these 2 different epimers are actually specifically known as anomers.

The specific epimer at the C1 position, the two different positions are called anomers. What we have is the alpha anomer, that's possible, and the beta anomer, that's possible. The alpha anomer for specifically with D-glucose, the alpha anomer is the one that faces the O down, meaning that the O must have attacked from the top because it attacked from the top and pushed the O down. The beta anomer faces the O up, which means that the carbonyl must have been attacked from the bottom so that it would push this O up. This explanation lies in equatorial preference. Do you guys remember the principle of equatorial preference in cyclohexane? And how larger groups like to be equatorial. See, how my O is equatorial? That is going to be part of the reason that this percentage is higher than that one because it likes to exist in the equatorial form. But guys, as much as I wish that was always true, there are exceptions to this and there are going to be some sugars that actually prefer the alpha anomer for other reasons.

The nomenclature has gotten significantly more complicated. A D-glucose with the penultimate alcohol facing towards the right, but once it cyclizes, it makes a 6 membered ring, therefore, D-glucose turns into D-Glucopyranose because this stands for the 6-membered ring. The beta is determined from the anomer. The system is simple: if the OH on a carbon in the Fischer projection of your monosaccharide faces right, it's going to point down in the ring; if it faces left, it will face up in the ring. Your last one, the penultimate one, the stereo descriptor does not follow that rule. If it's a D sugar, it's going to face up on the ring. If it had been an L glucose, then it would face down.

Draw the β-anomer predicted through the cyclization of D-mannose

• A.
• B.
• C.
• D.

Answer: (B)

Here’s what students ask on this topic:

What is the process of cyclization in monosaccharides?

Cyclization in monosaccharides occurs when the penultimate alcohol (the second-to-last hydroxyl group) nucleophilically attacks the electrophilic carbonyl carbon. This reaction forms a cyclic structure, resulting in either a furanose (5-membered ring) or a pyranose (6-membered ring). The carbonyl carbon becomes a new chiral center, known as the anomeric carbon, leading to the formation of two stereoisomers called anomers: alpha (α) and beta (β). The α-anomer has the hydroxyl group trans to the C5 carbon, while the β-anomer has it cis.

What are the differences between alpha and beta anomers in monosaccharides?

Alpha (α) and beta (β) anomers are stereoisomers that differ in the configuration around the anomeric carbon (C1) formed during cyclization. In the α-anomer, the hydroxyl group attached to the anomeric carbon is trans (opposite) to the CH2OH group on the C5 carbon. In the β-anomer, the hydroxyl group is cis (same side) to the CH2OH group on the C5 carbon. This difference in spatial arrangement leads to distinct physical and chemical properties for each anomer.

Why is the beta anomer of glucose more stable than the alpha anomer?

The β-anomer of glucose is more stable than the α-anomer primarily due to equatorial preference. In the β-anomer, the hydroxyl group on the anomeric carbon is in the equatorial position, which is more stable because it minimizes steric hindrance with other substituents on the ring. This stability is reflected in the higher proportion of β-anomer (about 64%) compared to α-anomer (about 36%) in aqueous solutions.

What is mutarotation in the context of monosaccharides?

Mutarotation is the process by which α and β anomers of a monosaccharide interconvert in aqueous solution. This occurs through the open-chain form of the sugar. When a cyclic monosaccharide dissolves in water, it can revert to its open-chain form, allowing the hydroxyl group on the anomeric carbon to switch positions. This results in a mixture of α and β anomers. For example, in glucose, mutarotation leads to an equilibrium mixture of about 64% β-anomer and 36% α-anomer.

How do you determine the configuration of hydroxyl groups in the cyclic form of a monosaccharide?

To determine the configuration of hydroxyl groups in the cyclic form of a monosaccharide, use the 'downright' rule. In the Fischer projection, hydroxyl groups on the right side of the carbon chain point down in the cyclic form, while those on the left point up. For example, in D-glucose, the hydroxyl groups on C2 and C4 are on the right, so they point down in the ring form, while the hydroxyl group on C3 is on the left, so it points up. The penultimate carbon's hydroxyl group follows a special rule: it points up for D-sugars and down for L-sugars.