Condensation into Disaccharides

Concept: Concept 1

8m
Video Transcript

What's up. Guys by now you should know quite a bit about monosaccharides but in this video I want to take a step further and define what a disaccharide is. So, let's get going with that. Guys a disaccharide is very simply going to be two monosaccharides that are linked by an O-glycosidic linkage in the middle. Remember, that O-glycosidic bond would just be at the anomeric posiition and oxygen attached to an R? Well, if you have that where the R group is actually a second sugar, that's called a disaccharide. Now, it doesn't matter whether it's an alpha linkage or a beta linkage, we'll get more into that in a little bit, that's just going to change the type of disaccharide it is but disaccharides exist in multiple different forms that are both alpha and beta, cool? So, guys the exact reaction that brings these two sugars together into one disaccharide is called condensation and guys the reason that we call it a condensation reaction is because back when we learn about the definition of condensation, what did it always mean, condensation always means that you take two molecules and you turn them into one bigger molecule with the release of water, you always have to release one water atom or one water molecule to count as a condensation and that's exactly what happens and the end product is that we form an acetal linkage, okay? Remember, we talked about acetals, I'm going to show you what the acetal looks like here, okay? Now, one thing that you guys should just keep in mind about disaccharide is that once you form a disaccharide those sugars are locked into position, so the typical type of mutarotation epimerization that might happen when you have a single sugar that cyclizes doesn't really happen anymore for disaccharides. So, what I'm trying to say here is that once you've formed your disaccharide it's kind of stuck in that position, it's not just going to go from alpha to beta and beta to alpha by itself okay, cool? So, let's just break down kind of each step of the reaction, let me explain this diagram to you. So, guys first of all we need two sugars. So, in this case I decided to bring two molecules of d-glucose together to form a disaccharide but guys I could have used pretty much any monosaccharides I wanted, this is just a very common example and it's a very easy example to look at but many different, the multiple forms are, multiple types of disaccharides exist using different types of sugars and using different types of linkages. So, here I'm just giving you an example. So, let's say that we wanted to form a beta 1-4 linkage between these two monosaccharides? Well, what would that even mean, why would we call it a beta 1-4? Well, guys first of all beta always stands for the first sugar and the relationship of the oxygen to the stereo descriptor carbons. So, remember guys that this would be my stereo descriptor over here, it's facing up and in this case this OH, because I'm using d-glucose this OH is also facing up so that means that these are cis to each other. So, this would be beta you guys remember that? Now, it doesn't have to look like this but this is just the one that we're using for right now okay? So, this is a beta d-glucose and notice that what I'm trying to do is I'm trying to form a linkage between the first carbon of my sugar 1 and the fourth carbon of sugar 2 and the way that we would count these guys is just like any cyclic sugar, we always count the anomeric position as 1 and then go around in a counter, in a clockwise way. So, then you would get 4 over here, does that make sense? So, if we were to bring these two alcohols together, the alcohol on one and the alcohol on 4, what we're going to get is the loss of water and the reason is because if you're trying to make an acetal linkage all you really need is one O, right? That means that, let's say, this is the O that stays, which is, okay? Actually that wouldn't be the O that stays, I'm sorry, So, let's say, this is the O that leaves, let's say this is the H that leaves and let's say this is the H that leaves, the O that stays is this one, right? This is the one and we can go through the mechanism later but that O will end up attaching to the carbon and notice that what we get as a by-product is one O and 2 H's leaving. So, we would get the condensation reaction and the release of one water molecule, okay? So, this condensation reaction would then link these two together and notice that what we would now get in terms of this linkage is we would get what we call a beta 1-4 because once again the linkage is going in the same direction of the stereo descriptor carbon and it's between carbon one is the first one and carbon four of the second one, okay?

Now, notice that two functional groups are present on this disaccharide, one we have an acetal, why do we call this an acetal because remember guys that the general formula for an acetal is that you have OR and OR connected to the same carbon and it's like a diether, is that a diether? absolutely, this is an acetal but notice that the anomeric position of the other sugar in this case is still exposed it still has an OH on it so that means that in this specific disaccharide I would have both an acetal functional group and a hemiacetal functional group present on the same molecule, this is going to be important later but for right now I'm just drawing your attention to it, okay? Now, last we have this name of cellubiose. So, you might be thinking, well, jhonny am I supposed to memorize that? maybe, it turns out that some professors and some textbooks and homeworks want you to know some, a few of the most important disaccharide you don't need to know all of them but you might need to know a few important ones, which I'm going to go ahead and talk about in a second but for right now what you should know or what you can just take, you take-home message from this, is that the disaccharide called cellobiose would specifically be the disaccharide that's formed from 2d glucose molecules making a beta one four linkage and if you were to change any part of that it would not be called cellubiose anymore, if you were to make it an alpha one four linkage, where now it's facing away from the stereo descriptor or if you were to change one of the glucose into a fructose, all of those changes would have massive impacts on the disaccharide, it would change the disaccharide completely and it would also change the name, okay? So, once again cellubiose is just the example that I'm giving for probably the easiest disaccharide to make, which is two d-glucose with a beta one four linkage, okay? So, in the next video what I'm going to do is, I'm going to talk more about important disaccharides that you might want to know

Concept: Concept 2

10m
Video Transcript

Now, I'm going to show you some of the most important disaccharides that you might need to know at some point and I also have them drawn out down here in this practice problem. So, as we talk about it I'm going to be referencing the drawing as well just so that it makes more sense. Now, guys disclaimer this list is not meant to be comprehensive, like I said, there are so many disaccharides out there and you may need to know more than these three and you may also not need to know any of them. So, I'm going to leave that part up to you, I'm just going to give you the information of the most importance I saccharides some of the most popular some the most cited disaccharides so that you'll at least see a few examples for later, okay? So, let's go ahead and start off with. Remember, that we've already discussed cellobiose, which would be 2 d-glucose with a beta 14 linkage. Well, what happens if you make 2 d-glucose molecules come together and condensate into a disaccharide but instead using an alpha 1-4 linkage. Now, what would that look like? Well, let's look down, this is actually the drawing. So, you can see that once they're going to have d-glucose, I'm just going to put d-glue and here I also have d-glucose and they look exactly the same but notice that now the anomeric position is faced trans to the stereo descriptor this one is going down, this one is going up, that's the definition of an alpha linkage but notice that everything else is still the same, I have the 1 and the 4 linked together, so notice how guys first of all the shape of my disaccharide has completely changed, before the shape used to be a nice straight chain and now it got like a little bit of a kink to it, that's going to be important, those kinks and those straight edges and all those kinds of structural changes actually significantly impact how these sugars react in Physiology, in the human body, it may determine if it can be digested or not but anyway guys what's interesting is that now if you just change that one little thing you've now made maltose, so the maltose is the name of a cellobiose, don't quote me on that because it's not technically true but it would be the same thing as cellobiose but instead of beta it's alpha, cool? Awesome. So what else? let's go to another one, well, what if you want to keep the one, let's say you want to keep the beta 1-4 linkage like we had for cellobiose and you want to keep sugar 2 as d-glucose but now we want to change sugar 1 into d-galactose, which is just going to differ by the few positions of OH's facing up or down, let's go down, let's just see this for a second, so this is what it would look like. Notice that once again my linkage now looks just like cellobiose, right? I have my one position, I have my four position, it looks like a beta once again. So, they beta one four and notice that this is also a d-glucose over here, the only difference is that something looks a little bit weird on the one sugar one. Notice that this OH is facing up instead of down, that's the only difference. So, instead of having it go down like a normal d-glucose it's now going up, that's the only difference. So, basically this is a cellobiose where the alcohol in position four is going up making it a galactose? Well, guys now we've just made lactose, okay? So notice that just these small tiny little changes will completely change the sugar, will completely change the disaccharide, okay? And then finally one more that's just really important that you need to know is a d-glucose plus d-fructose, this isn't, this isn't much different than the others. So, remember fructose would actually be usually a five membered ring with an alpha 1 beta 1 linkage. Now, what does that mean? Well, notice that I'm using two completely different types of chains, so the reason that we call it an alpha 1 beta one is because, let me show you, because the fact that over here, this is a beta 1 because for the, what sugar is this again? for the d-glucose. Notice that it looks, I'm sorry, this is an alpha 1, this is my alpha one because notice that it's facing opposite to the stereo descriptor, the stereo descriptor is this way. Notice that this O is facing down so the alpha one comes from the d-glucose, right? For the flip fructose, we call this a beta 2 because the one position of fructose is actually this carbon here, okay? So, that's the one position, so this is my 2 position so that means that it actually touches the 2 and it's beta 2 because the stereo descriptor of fructose is this one right here. So, do you have to absolutely memorize this right now? probably not but I want to expose you to the fact that sucrose, which is the one I'm sensing at here, which is a very, very important disaccharide is made by two different types of linkages, it's like a linkage that you have to describe with two letters because you've got the Alpha 1 and the d-glucose and you pull up the beta 2 on the fructose and you have to describe both of those, you wouldn't just call it alpha you wouldn't just call it beta, you'd call it a combination of the two, okay? And, this is called sucrose, okay?

Now, guys fun fact, which is related to these and it's actually going to be important later. So, just keep this in mind, humans cannot, cannot digest carbohydrates or disaccharides with O beta glycosidic linkages, okay? So, remember that we were talking about the difference in structure between beta and alpha, alpha has more kinks, beta is more straight usually, those straight ones the human body can almost never digest because they're too rigid, it's too difficult to get the enzymes in there. So, we can't digest it, except for one important exception, can you guys think of what's that exception might be? it's on this page, lactose some people can they dust lactose and some can't. So, when you hear that someone is left intolerant that's just because that person's normal most, humans cannot digest beta glycosidic linkages, that's our default evolutionary state, is that we would not be able to digest lactose, the reasons for that are severe it make a lot of sense, that once you're past like the age of 1 or 2 your body stops making that enzyme called lactase. So, I'm just going to put here lactase is the enzyme, lactase is the enzyme that digests, that breaks down lactose into its monosaccharides, your body stops making it because it thinks that you're not going to drink any more milk, right? So, it thinks, oh we're done. Now, we're going to eat real food but now the modern American diet or even global diet, we're drinking cow milk and all these dairy products more than ever before. So, our bodies aren't adapted to that because they stop producing lactase a long time ago and a lot of people are struggling to digest lactose because of those beta glycosidic linkages. Now, another fun fact on top of that, whenever you get lactose free milk, it's not really lactose free they didn't take out the lactose, because that's actually the milk sugar, all they did is they added in lactase into the milk so that you would be able to digest it since you don't make your own lactase, they added in some extra lactase. So, it's actually a big lie, lactose free doesn't mean that doesn't have lactose, they just added the enzyme so that you can digest the beta glycosidic linkage, cool? So, interesting, right? So, if you have to predict, which of these the body or human body would be able to use as energy, which you know would they be? maltose and sucrose because both of those contain to some extent alpha linkages and alpha linkages we can digest, they're easier to digest force, the beta linkages, we need a little bit of help, with lactose and for other types of disaccharides we just won't be able to digest them at all. So, for example, cellobiose you absolutely cannot digest, that's too fibrous for us because it's so rigid. So, even you would never eat cellobiose, that's more use for like structural elements and stuff like that, cool? Awesome guys, so let's go ahead and move on to a practice problem.

Problem: Identify the following disaccharides as reducing sugars (RS) or non-reducing sugars (NS)

4m

Concept: Practice 2: Draw a mechanism for the condensation of D-Glucose into cellubiose

10m
Video Transcript

Draw a theoretical acid-catalyzed Fisher glycosdation mechanism for the condensation of d-glucose, that's 2 d-glucsose molecules into cellobiose. Note this reaction would lead to actually very poor yields of cellubiose, can you hypothesize why, cool? So, that's first things first, let's just get this mechanism down on paper and then we can talk about the theory of why this wouldn't work so well, okay? What do we know about Fischer glycosydation? it's an acid catalyst mechanism. So, let's just go ahead and stick some acid in here, I'm going to go ahead and use H3O plus and what we know is that, what we're going to try to do is we're going to try to get rid of this OH. Remember, that according to the mechanism we're trying to get rid of that OH and get the new OR to attach. Now, that new OR group usually it's just like a methanol but in this case it's going to be an entire sugar. So, I'm going to get that whole sugar to attack, let's go ahead and draw out step by step, what the mechanism would be and remember that all this can be found in your O-glycosidation videos. So, oxygen grabs the H, we're going to protonate and let's go ahead and draw this out and if you guys don't mind I am going to copy this, so that the video goes a little bit faster, onto my clipboard so that I can use this sugar in the rest of the video, you guys can pause if you are having a hard time following on, cool. Awesome, cool? So, I don't have to keep drawing that sugar over and over again. Great, so we know that here, I would have a proton and a plus charge and this is where I can now, make my, I have a good leaving group and I can kick it out using my O and what that's going to give me is a new sugar? Well, a new sugar derivative and it's actually my intermediate it's the most important intermediate probably of this chapter because what I will end up getting, this is called my oxocarbenium cation, okay? The oxocarbenium, remember, it's the reason that we've only react at the anomeric position and no other positions because we make this resonance stabilized intermediate with the O, cool? So, then I'm just going to draw that the resonance structure would be either plus on the O or plus on the carbon, let's go ahead and just bracket that off, cool? So, that's my oxocarbenium, and now what we know is that we want instead of just methanol or some random alcohol to attack, we actually want to attack is the four position of my second sugar, and remember the reason is because cellobiose is what kind of linkage, if you don't have this memorized, it's fine, but remember, that cellobiose would be a beta 1-4 linkage. So, I'm looking for the 4 position of my second sugar to come in and attack, cool? So, let's go ahead and fix this up, I'm going to use this version of the intermediate, which is the plus here, because it's just it's the easiest one to work with and it's easy to visualize that this O can now come from the top and attack that positive. Now, could it also have come from the bottom? totally but that would not be beta 1-4 anymore, if it came from the bottom, what would that be? alpha 1-4, because of becoming opposite to the stereo descriptor, it would then be going this way, but in this case I'm trying to make the beta 1-4. So, let's go ahead and draw that the arrows coming from the top, cool? So, now what I'm going to get, oh, I should have used this whole time, make sure that we're using the correct arrows guys, these are equilibrium arrows because this is all reversible, it's all acid-catalyzed. So, now what I'm going to get is this and actually, this is going to work out nicely, I'm just going to erase this one here, erase this H. Remember, that that's my water, right? So, I'm actually drawing, this is the condensation mechanism, I'm losing water and now we can just reposition this guy, I know you wish you could do all these things, it's okay though, you can pause, Sool. How awesome is that? So, we just lost our water and we just made our beta 1-4 linkage but remember that we're going to have an extra H, oh I already put that we lost our water. So, when you draw that you lose your water like that, that's not really a mechanism, it's more a formula, it's just showing you the progress, I'm going to go ahead and erase this because we haven't lost our water completely yet, what we actually have lost is a water and now we're about to lose an H to regenerate the acid, okay? So, then finally, I have water here, by the way, this is the water that we lost earlier and now I'm going to attack that H, and now I'm going to get my product and my product would be the cellobiose.

Now, guys just, I don't think I was very clear with what I just said and what I was just saying is that if a professor wants every single arrow you can't just put lose water and condensate, okay? Because, that's not providing every single arrow, you would have to do it the way that I just did it now, which would give you your final product here, okay? But a lot of times professors and textbooks and homework problems take shortcuts and they don't throw the whole mechanism, they'll just draw like, oh, these two sugars come together, you lose water and you get the final answer here, which is also acceptable but it's just like a shortcut to the mechanism. So, in this case I didn't want to take the shortcut, I wanted to do with the legitimate way so that you guys, in case you have to draw it this way now you know how, cool? So, there is our entire mechanism, let's just draw this reversible arrow as well, and now let's go back to the other question, which is why do you think this would lead to a really poor yield of cellobiose? and guys it's actually pretty obvious, poor yields due to, what do you guys think? I hear you saying it, you're not using the same words I'm going to say but I think you got the point, mixture of linkages, right? You get a mixture of linkages because we just drew the beta 1-4 but you would get a mixture, let me just put like one for like point number one, you get a mixture of alpha and beta, which means that if you were just to link at the 1-4 position that would be a mixture of maltose and cellobiose. So, already you're at like at half and half right there, right? But then you'd also get a mixture of positions, right? So, right now I just got a 1-4 but it could've also, I could have gotten a 1-2 linkage, right? Or a 1-3 linkage or a 1, or a 1-6 linkage, all of these can be seen in different sugars, so right now we drew this happen to be the beta 1-4 because I was asking for cellobiose but it's very, very, if I were to just react this an acid all these different permutations would happen, which would mean that I would have almost no cellobiose and I would just have a big conglomeration of disaccharides and trisaccharides and they would all just be kind of like intermingling and it would just not be a great synthesis. So just, so you guys know you might be saying. Well, then how do you make that saccharides? Guys, that's for a different video. The proper synthesis of disaccharides in the lab, if you're a sugar chemist, you're going to have to use protecting groups, you're going to have to use very special reagents that make sure that everything goes where you want, if you're, if it's in the human body, you have enzymes to make sure that you do that, you have specific enzymes to make sure that you make exactly the right disaccharides but if you're in the lab you can't just throw this with some acid and expect to get cellobiose, you're going to get a mixture of everything, okay? So, guys, I hope that made sense, let's go ahead and move on to the next page.