Monosaccharides - N-Glycosides - Online Tutor, Practice Problems & Exam Prep

N-glycosidation involves the reaction of monosaccharides at the anomeric position with nitrogenous nucleophiles, forming N-glycosides or glycosyl amines. This process is crucial in creating ribonucleosides, which consist of ribose and a heterocyclic nitrogen base, forming the backbone of RNA. The four bases in RNA—guanine, cytosine, adenine, and uracil—are linked to ribose via an N-glycosidic bond, specifically a beta N linkage, essential for RNA structure and function.

General Reaction

Hey guys. Now let's talk about an oocyte reaction of monosaccharides called N glycosidation. So guys, monosaccharides have the ability to react at the O position or the oxygen position in several different ways. In acidic conditions, monosaccharides can substitute selectively at the anomeric position, only at the anomeric position to produce what's known as glycosides. Remember that glycosides would put basically like an R group or some kind of substituent over in the anomeric position. Okay? Well, it turns out that when nitrogenous, so I'm just going to put n for nitrogenous nucleophiles are used, meaning nucleophiles that get their lone pair or their nucleophilicity from a nitrogen, that substitution product is called an N glycoside. Okay? Because instead of forming an O glycoside meaning that you have a glycoside with an oxygen here, instead, we're going to form a glycosidic bond with a nitrogen-containing compound, okay? Now the term I'm going to use most of the time for it is called an N glycoside. That's very similar to O glycoside so it's very easy to remember. But another nomenclature term that you should just know is that N glycosides are also referred to as glycosyl amines, okay? So if you hear about glycosyl amine or glycosyl amine, That is basically an amine being attached to, to a ring, to a furanose or a pyranose, and it means the same thing as N glycoside. Okay? So as you can see in this reaction that I'm about to show you, this molecule could either be named 1 Amino D Glucopyranoside, because I'm saying that the glycoside is an amino group, 1 amino, or it can be referred to as D-glucopyranosylamine because what we're saying is that it's the same as a glucopyranose, except that it happens to have an amine in the anomeric position which is a pyranosylamine, okay? Guys, I'm not going to make you're not going to be accountable for this nomenclature, but you should still recognize it, okay? Awesome. So let's go through the general reaction. The general reaction says that if you take a cyclic carbohydrate and then you react it with a nitrogen-containing nucleophile. In this case, I'm using the simplest one which is ammonia, but it could have been a complicated one. In acid, what we're going to get is that the nitrogen attaches to the anomeric site and only the anomeric site, and you're going to get a mixture of anomers with that nitrogen in the glycosidic bond, this is called the N glycosidic bond. Glycosidic link or bond. Okay? I just want to make some points here. So just you know, why can it only react at the glycosidic position and no other positions? Why would you only substitute the n here and not for example at C2? Guys, for the same exact reason, same exact mechanism as O glycosidation. Remember that in order for O glycosidation to take place, you need to pass through the oxocarbenium intermediate that stabilizes the positive charge right here. The same exact thing is going to happen with N glycosidation Glycosidation where acid is going to come in, kick out the water, I'm going to form a double bond, and but all that happens with N glycosidation is that at the last step nitrogen comes and attacks the positive charge here and then gets deprotonated. And that is why we would get a nitrogen-containing compound that looks very similar, just at the anomeric position. Cool? Awesome. So that is that so far. In the next video, I'm going to talk to you guys about specific types of N glycosides that are called Ribonucleosides.

Creating Ribonucleosides

So an N-glycoside that specifically contains a ribose monosaccharide along with a heterocyclic nitrogen base, meaning it needs to be like an aromatic nitrogen-containing heterocycle. If you have those things connected through an N-glycosidic bond, which we just talked about, that is actually referred to as a ribonucleoside or also just like to be called a nucleoside. Okay? Now keep in mind that's a very different word than the one we had up here, not glycoside. Glycoside is this, but if it's specifically a ribose with a heterocyclic nitrogen base, it's called a ribonucleoside which happens to be the r and n portions of RNA. RNA genetic material, nucleic acids are actually just made out of a sugar backbone along with the nitrogenous base. So remember that RNA stands for Ribonucleic acid. Right? And what we're doing here is we're forming the ribo and the nucleoside part. Okay? The only thing is that later on they add phosphate groups, you add phosphate groups to get to the acid part. Okay? So how does this work? Well first of all guys, I'm going to be showing you the 4 base pairs of RNA because that's the easier one to talk about first.

So you guys might remember this from biology, you may not remember this from biology which is fine, I'm just going to teach it from scratch. But basically, the 4 heterocyclic bases that you could have for RNA are guanine, cytosine, adenine, and uracil. And these are represented by the letters g, c, a, and u. Now you might remember that there's a letter called t, you might be more familiar with t but T works with DNA and it's very similar to uracil, it's actually just missing it has an extra methyl group, that's it. But just knowing these bases you pretty much have the big picture of what a base looks like, okay? And the way that RNA works, the way that it's built is that you have a ribose sugar, remember ribose is alright. So we have D-ribose and D-ribose cyclizes to create alpha D-ribofuranose, which it doesn't always have to be alpha, but alpha happens to be the prevalent one for this one, okay? So alpha Dribofuranose. By the way, the reason this one's alpha is because notice that the stereo descriptor is facing up in this case because it's a D, so it's facing up. So then since it's trans that would be alpha. Okay now guys what happens is you take that furanose, that ribofuranose, and you attach it with an N-glycosidic bond to any one of these heterocyclic bases either guanine, cytosine, adenine or uracil.

In fact, just you know the nitrogens that we would use would be these. It's either going to be this nitrogen for guanine and adenine or it's going to be this nitrogen for cytosine and uracil. Okay, so these are the nitrogens specifically that attach to the anomeric position. And if you make that beta N1 linkage, what you're going to wind up getting is what's called a ribonucleoside. In this case, ribose comes from the fact that it's a ribosugar. Nucleoside because it's now attached to a heterocyclic base, okay? Now let's just break this down a little bit so you guys know exactly what I'm talking about. Why do they call it a beta N linkage? Well the N comes from the fact that it's an N-glycoside, right? Where does the beta come from? Why is it beta? Because specifically beta is the direction, is the anomer that faces cystowards our stereo descriptor, right. Notice that my stereo descriptor is facing up and this one is facing up and actually to be RNA, you need to be the beta anomer. The alpha anomer doesn't work, it needs to be the beta anomer. They need to both be facing up. So in this case, this ribonucleoside is the basics of the base code G. G later on, all it needs is a phosphate group, phosphate groups attached to the O and you're actually going to have RNA. Okay. Specifically, it's called guanosine once you attach the ribosugar to guanine. Isn't that cool? So guys, even though this seems a little bit like a little bit advanced, like it seems like, oh wow we were just talking about sugar and now I have like a whole RNA molecule that I'm dealing with. You guys know this whole mechanism. There's no reason that you can't build one of these from scratch now because we know how to use the anomeric position oxycarbenium ion that then can get attacked by the nitrogen. So really this is just a cool application of a mechanism you already know, alright? So let's go ahead and move on to the next video.

Propose an acid-catalyzed mechanism by which cytosine can form a β-1 N-linkage with 2-deoxy-β-Dribofuranose to produce a deoxynucleoside (DNA) called deoxycytidine.

Propose an acid-catalyzed mechanism by which cytosine can form a beta-1-N linkage with 2-deoxy-beta-D-ribofuranose to produce a deoxynucleoside or DNA called deoxycytidine. Guys, this sounds so hard, but it's actually not that hard, okay? We're just going to go step by step, okay? First of all, we have to propose an acid-catalyzed mechanism. We're already given what the product looks like. So we know at some point this nitrogen that's in the one position on my cytosine has to come in and be attached to the top of the anomeric position there, and then it makes this. So really, this isn't that bad, we just need to draw out what the mechanism would look like, okay? Now I do want to find some stuff really quick, some terminology before we get started. First of all, I called the linkage a beta-1-N linkage. Why is it called that? Well, let's look at the final product. We're talking about a beta anomer. So that's a beta linkage. It's an N linkage because it's an N-glycosidic bond. And specifically, the reason it's called beta-1 is because it's attached to the one position of my cytosine. So it's a beta-1-N linkage because the nitrogen that is attached to the carbon happens to be in the first position of that base. You don't need to know how to number bases ever, okay? I mean, not in this course, maybe in biochemistry later. But right now I will always, or you will always get the numbering for the bases, okay? They don't always attach in the one position. For cytosine, it does, but for other bases, it will be another position, okay? Cool. Second piece of terminology, 2-deoxy. The actual sugar, ribosugar that we're using is not a regular ribofuranose, it's 2-deoxyribofuranose. So why did I include that? Well guys, it turns out that this is a modified monosaccharide. Remember, to be a monosaccharide, you need to have oxygens at every carbon. This carbon is missing an oxygen, so is it a monosaccharide? It's not; it's not like a true unmodified monosaccharide. So it turns out that in biochemistry, DNA is missing the O at the two position. So that's why it's called DNA. DNA is deoxyribonucleic acid. It's missing the O in that 2 position. So the reason that I put it there is because I want you guys to see what DNA would look like. DNA is always missing that O, it makes it much more stable if it doesn't have that O there, which is why. But just you know it's like a modification of a monosaccharide, but it reacts exactly the same. Obviously, you can't epimerize this one, right? You wouldn't be able to switch the 2 positions; that's a difference, okay? But in terms of this mechanism, it's going to work exactly the same as regular glycosylation. So let's go ahead and actually get started. So let's go ahead and redraw this structure. Oh, and the first step, guys, would be to use acid. I'm just going to use H3O+ because it's my favorite. And

Here’s what students ask on this topic:

What is N-glycosidation in monosaccharides?

N-glycosidation is a chemical reaction where a monosaccharide reacts at the anomeric position with a nitrogenous nucleophile, forming an N-glycoside or glycosyl amine. This reaction occurs under acidic conditions and involves the substitution of the anomeric hydroxyl group with a nitrogen-containing group. The process is similar to O-glycosidation but involves nitrogen instead of oxygen. N-glycosides are important in biochemistry, particularly in the formation of ribonucleosides, which are essential components of RNA.

What are ribonucleosides and how are they formed?

Ribonucleosides are molecules consisting of a ribose sugar and a heterocyclic nitrogen base linked via an N-glycosidic bond. They are formed when a ribose monosaccharide reacts with a nitrogenous base (guanine, cytosine, adenine, or uracil) at the anomeric position. This reaction creates a beta N linkage, which is crucial for the structure and function of RNA. Ribonucleosides are the building blocks of RNA, with the ribose providing the sugar backbone and the nitrogenous base contributing to the genetic code.

Why does N-glycosidation occur only at the anomeric position?

N-glycosidation occurs exclusively at the anomeric position due to the formation of an oxocarbenium ion intermediate during the reaction. This intermediate stabilizes the positive charge at the anomeric carbon, making it the most reactive site for nucleophilic attack. The nitrogenous nucleophile then attacks this position, leading to the formation of an N-glycosidic bond. This mechanism is similar to O-glycosidation, where the anomeric position is also the site of substitution.

What is the significance of the beta N linkage in RNA?

The beta N linkage in RNA is significant because it ensures the correct orientation and structure of the ribonucleoside. In this linkage, the nitrogenous base is attached to the ribose sugar in a beta configuration, meaning both the base and the stereodescriptor (usually a hydroxyl group) are on the same side. This configuration is essential for the proper formation and function of RNA, as it allows the ribonucleosides to form the correct hydrogen bonding patterns and maintain the stability of the RNA molecule.

What are the four nitrogenous bases in RNA and their corresponding ribonucleosides?

The four nitrogenous bases in RNA are guanine (G), cytosine (C), adenine (A), and uracil (U). When these bases are attached to a ribose sugar via an N-glycosidic bond, they form the corresponding ribonucleosides: guanosine (guanine + ribose), cytidine (cytosine + ribose), adenosine (adenine + ribose), and uridine (uracil + ribose). These ribonucleosides are the building blocks of RNA, contributing to its genetic coding and structural properties.