Lecture 16. Introduction to Carbohydrates: Structure and Stereochemistry.
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Nowick, James
This is the third quarter course in the organic chemistry series. Topics covered include: Fundamental concepts relating to carbon compounds with emphasis on structural theory and the nature of chemical bonding, stereochemistry, reaction mechanisms, and spectroscopic, physical, and chemical properties of the principal classes of carbon compounds. 
 All right, give yourselves a big hand. We've done five quizzes in the class. We've got one last one to go, which is sort of a bonus in the sense that I dropped the lowest quiz. We've also gone through what I consider to be some of the most intellectually challenging material of the course. We brought in ideas of mechanism. We brought in ideas of synthesis. And now we're kind of winding up the course. And I want to cover some topics that are, I think, more interesting and in some ways bring back some old themes and bring in some new themes as well. So we're going to spend today, and we're going to spend Thursday talking about carbohydrates. And carbohydrates, in one way, is a very old topic in organic chemistry. Carbohydrate sugars are central to so much of life. They are, of course, the sugar that you put in your coffee. They are the glucose and fructose that make up that sugar. They are the components of starch and cellulose. In other words, paper on your desk and the cornstarch and so forth and potato starch in the vegetables that you eat. The backbone, along with phosphate, sugars, ribose, or the backbone of DNA, they're attached to many biologically active natural products. Sugars coat the surfaces of your cells. Your blood types are determined by which types of sugars. You have on the surface of your blood cells, and in turn give you antigenicity, give you an antibody response to getting the wrong sort of blood type if you get an infusion. So sugars are fantastically important. We are coming back to an old theme that you learned in 51A, and that's stereochemistry. I think the toughest thing about learning sugars isn't the stereochemistry. It's the different representations and interrelationships. We're going to spend some time today talking about structure and stereochemistry of sugars. I spent last night and this morning making some special tools for you to help understand some of the representations that are often used. Personally, I'm a big fan of plastic models. For the Darling models you used in 51A and maybe in some of the so-called dry labs associated with your course, and I recommend you bring them back to learning this chapter. Oh, no, I see tears here from the models. You can also use your computer. I will let you use models on the final exam, so it's useful to have them, plastic models. So it's useful to have them complement things. All right, I want to start with literally a simple sugar with sort of the most fundamental or maybe the most common sugar, and we're going to draw it in a chair conformation. The sugar that I'm drawing here is glucose. It's kind of easy, I like it, because when I draw my chair like so, all of the substituents are in the equatorial position, so it's very easy to remember the structure of glucose. Now sugars have an aldehyde group, and we're going to talk more in a second, but for the most part they exist as cyclic HMI acid towels. I'm going to draw, we have another stereocenter for a cyclic HMI acid towel, and I'm going to draw that hydroxy group at this position, at the one position that we'll learn is called the anomeric position. I'll draw it equatorial. This molecule is called beta D glucose, and so it's a member of the class of carbohydrates I guess if you go to the gym you might call them carbs of course, it's a nickname. Its molecular formula is C6H12O6, and if you think about it, then the reason it gets its name as a carbohydrate is that the formula is carbon plus H2O, and literally if I take some sugar, if I take some table sugar, and I take sulfuric acid which is very dehydrating and can yank all the water out and carry out a whole bunch of reactions. If you've ever seen this done, you just put it in a beaker, pour in, put some sugar in a beaker, pour on some consulfuric acid, and this big snake of carbon comes out of the beaker, this big rod of frothy carbon and sulfuric acid along with a little bit of smoke and so forth. Anyway, I'm not going to do that demonstration here in part because it's kind of hazardous, but it's a lot of fun. Aldoes is a member of a class of carbohydrates, a broad, broad class of carbohydrates that we call aldoes. The reason we call it an aldose is that when we go ahead and unwrap the structure, when we break up the hemisetal at the one carbon, you get an aldehyde. There are also sugars where if you break up the hemisetal, you get a ketone, and those are called ketosis. We'll talk about those later. Glucose is a six carbon sugar. We number it from this position, one, two, three, four, five, six, and so glucose is called an aldohexose, hex is six. I guess to be consistent, I will write an aldose to indicate it's one of many, many. There are a bunch of other things things get called because glucose has a six-membered ring containing an oxygen in the closed form, in the hemisetal form. We call it a pyranose sugar. Pyran is a six-membered ring containing an oxygen atom. Tetrahydropyran is a saturated six-membered ring containing an oxygen atom. Glucose is a derivative of tetrahydropyran, so we call it a pyranose. The other important ring containing oxygen is a five-membered ring containing an oxygen, the aromatic compound with double bonds, and it is called furan. If you have all hydrogens on the ring, if the ring is fully saturated, you call it tetrahydrofuran. We've seen that THF is the solvent, and so there are other sugars that have five-membered rings in them that you would call a furanose or a furanose form of the sugar. And I guess as long as we're talking about names here, we would also refer to glucose as a monosaccharide. Glucose, of course, means one saccharide, well, sugar. I want to give us some contrasts in structure and in stereochemistry by drawing a disaccharide at this point, and it's going to introduce some basic concepts here. So we're going to start with drawing another pyranose form of a ring. We're going to have two of these linked together, so two chair cyclohexanes. And I'm going to go ahead and draw everything the same on this ring as I did for glucose, except at the four position, I'm going to, instead of having the hydroxy group in the equatorial position, I'll put the hydroxy group in the axial position. We're going to make molecule with two sugars in it. It's one that you might have consumed this morning. One that actually is good for you. Well, maybe I guess all sugars are okay in moderation. Okay, so we're going to link to another ring here. And this ring we'll have as a glucose type ring, like so. So here's our disaccharide. Disaccharide is lactose. I guess my drawing isn't the prettiest in the world. I'm always delighted when I look at people's notebooks and see they're drawing so much prettier than mine. So lactose is a disaccharide. And I think there are a couple of interesting take home messages that we get from this. First of all, sugars can be linked together, one to the next, to the next. Much for example is a long, long chain of sugars as is cellulose, basically a polymer of almost infinite length. Now you might look and say, well, it's a little different looking than glucose. I mean, we basically formally removed one water molecule. So if you write out the molecular formula of lactose, it's C12H2O11. And so you'd say, well, we don't have the same ratio of carbon to hydrogen as we had because we've connected in glucose. But if you notice, it's still carbohydrate. It's still effectively carbon plus H2O. And in this case, 12 carbons plus 11 H2O's. In the case of glucose, 6 carbons plus 6 H2O's. So if you look at our lactose, as I said, we have two units in it. We have our glucose unit. And now we have another sugar unit in it. This is a galactose unit. So galactose, let me draw out galactose and glucose in just a second. But I just want to make one last point. We have a linkage from the one position of glucose, right? So this is the one position. And then to the four of the one position, I'm sorry, of galactose, and that's the four position of glucose, right? We number our way around the ring, 1, 2, 3, 4, 5, 6. And so we call this a 1 to 4 glycosidic bond, glycosidic linkage, or glycoside bond. I want to draw out the units, the subunits here in galactose. So I'll draw out the two sugar units. I'll redraw glucose again. It pays to practice a little bit in your drawings. And I've got to say I'm no artist as far as cyclohexane rings go. Basically, the theory is you're going to be making parallel lines for the equatorial bond for this OH group is parallel to the CO bond for this one. The equatorial bond to this OH group is parallel to this one. As I said, I'm not much of an artist, but I can get my ideas across competently. All right, so galactose, so this is glucose, or more specifically beta-D glucose. We'll talk about what that D means in a second. And now we'll draw galactose, more specifically beta-D galactose. I'll talk more about that beta in a second. All right, so everything is the same over here except as I was indicating when I drew our molecules, now we have a different stereochemistry at the four position. So two isomers that have the same connectivity, all of the same atoms connected together in the same way, but just differ in the stereochemistry of one position are diastereomers. They're stereoisomers that are not enantiomers. Remember when you learned about stereochemistry, you learned about enantiomers, compounds that are non-superimposable mirror images. You learned about diastereomers, stereoisomers that are not enantiomers, and then you learned about constitutional isomers, molecules that have different connectivity, different arrangements of atoms. All right, at this point I want to draw another structure and I'm deliberately proceeding reasonably slowly and methodically here because I think it really takes some time to bring all these ideas into your head and to dust off the cobwebs on some of the stereochemistry and structure that you learned back in 51A. So I'm going to draw a different structure here. We're going to do everything the same as glucose with one exception. I'm going to now, instead of having our stereochemistry at the one position be equatorial instead of having the hydroxy group at the one position be equatorial, I'm going to have our hydroxy group at the one position be axial. Now this is alpha D glucose and in the convention of organic chemistry you have beta as the up position, the top face of the ring, alpha as the bottom face of the ring. So the OH is pointing down to the bottom face as we've drawn it at what we call the anomeric carbon. So the carbon that makes up the hemiasatow is very, is occupies sort of a privileged position if you think about it because unlike all the other positions your stereochemistry there depends just on how you've closed the hemiasatow whether you've closed it so that the OH group is equatorial or axial. And so because of this very special diastereomeric relationship in sugar chemistry we often have yet another word for diastereomer involving the hemiasatow to labile position so we call it, we give it a special name as I said this is the hemiasatow position and so we call this ananomer. So just as we would say that beta D glucose and beta D galactose are diastereomers we would say that alpha D glucose and beta D glucose are anomers they have a special diastereomeric relationship to each other. They're still diastereomers but they're a special type of diastereomer that often gets called ananomer. So I'll write that down. Okay. So most diastereomers are stereochemically stable in other words if I have a bottle of lactose and I go away and go away for a long time and travel around the world and come back I still have a bottle of lactose it would never become a bottle I'm sorry if I have a bottle of galactose it would never become a bottle of glucose. If I have an aqueous solution of galactose it is stable as galactose. But this is not the case for anomers in which you have a hemiasatow. We've already learned that hemiasatows are not stable compounds they are in equilibrium with aldehydes. Now in the case of cyclic hemiasatows we learned that they tend to favor the closed conformation. In the case of glucose that's really, really, really strongly a preference and nevertheless at equilibrium you have a teeny tiny bit of the aldehyde form of the open form. In other words alpha and beta D glucose can interconvert in water and exist in equilibrium. So I'll write this as an equilibrium I'll say in water because in the solid state the crystal lattice keeps them stable but in water you have all sorts of chemistry occurring involving carbonyl groups and so the alpha and beta forms of D glucose can interconvert at equilibrium you have a 36 to 40 to 64 ratio. And I want us to think ourselves through this interconversion process and I'm going to sketch it out here in our mind's eye. So I'll start with alpha D glucose. We're not going to write a detailed mechanism. I think by this point I'm hoping that you are on top of carbonyl chemistry enough to be able to work through the mechanism. Remember in the case of a cyclic hemiacetal catalyzed by acid or by base but we'll think acid and even in water you have a little bit of acid you have 10 to the negative seventh molar H3O plus in neutral water. You can protonate all your oxygen atoms. If you protonate this oxygen atom you can open the cyclic hemiacetal and so I'll write a tautomer here. I will write the isomer in which we've opened this linkage and so now we have our aldehyde. Everything else is the same. So we've just opened our linkage here to form the aldehyde. Remember mechanistically you can think of protonate on this oxygen, push electrons down, kick out that oxygen. Now you have an oxocarbenium ion, take off the proton. All right now if we imagine rotating about this bond here like so and I'm just going to say we're talking equivalent structures here. Generally when you rotate about a bond you don't think about a structure as being different you think about it as being a related as just being a rotomers. So I will rewrite rotating about the bond here like so. So all I've done differently now is rotate about the bond to the aldehyde. And now if you imagine closing up the structure here so we've started with alpha D glucose. We've envisioned opening it to form the aldehyde. At equilibrium here you have about 0.003% of the open form at equilibrium. And now if you imagine just re-closing this we've gone to the beta form. We've gone from the alpha anomer to the beta anomer. Question. Can you do that for lactose? Great question. Yes and no in the linkage. So the question is very, very good. And I'm glad you asked it. Okay. Oh lactose, not, yeah lactose, right. Absolutely very good question and I am delighted, delighted that you asked it. So let's go back to our lactose structure. Alright, in our lactose structure there are two types of anomeric carbons, two types of carbons at the one position. There's this carbon which has a hemiasatal and then there's this carbon here which has an acetal. Remember a hemiasatal has a hydroxy group on it. An acetal doesn't have a hydroxy group on it. And so the hemiasatal form absolutely can equilibrate. And so the structure that I drew for lactose that's in your milk and whatever you drink in the morning on your cereal, cream in your coffee, the lactose that's there, the lactose that's in your ice cream has an equilibrating mixture of the beta and alpha anomers in the glucose unit. However, unless you have strong acid and by strong acid now I don't mean neutral water or a little bit of dilute HCl but unless you have a very strong acid that can break apart an acetal, boiling HCl solution or boiling acid, the linkage, the beta linkage off the lactose unit is stable and doesn't undergo interconversion. So I will write stable over here and when something interconverts we say it's labile for this position. Good question, good thought. Other good questions? Can a galactose have a carbon one like a steric shift and if so like a wool type molecule because? Can galactose, so the galactose unit, this subunit here at carbon one free galactose, absolutely. Okay, great, another great question. So, and I want somebody to answer for me here so we saw that we had, I drew the beta compound, what do we call this form of galactose? Alpha. So this is alpha D galactose and I'm going to tell you something else right now. So it's really good to have a few pieces of core knowledge that you keep in your head because you use those. We've done this with, when we talked about pKa's I talked about, yeah I know the pKa of a ketone, call it 20 whether it's a ketone or an aldehyde, know the pKa of an ester, know the pKa of LDA. That core knowledge is very useful because you can build on it. There are lots and lots of different monosaccharides. I do not, in my own head, I'm not a practicing sugar chemist, keep all of the structures of all the different monosaccharides. I could if I wanted to but it's just not useful for me. But glucose and say the one diastere, one diastere or galactose are useful things to know because it's something that you can hold on to and then you can build on it. So when you see various other sugars, you see tallows or something, you can understand relationships to them. Other questions at this point? Yeah? Why is it that if you change the position at the one group, if you change the stereochemistry at the one position, it's not a different sugar and if you change it at the four it is. The same basic idea because alpha and beta D glucose are labile because they interconvert. We'd say they're rapidly interconverting, they're interconverting, they're the same basic molecule. But for ones where you have stable diastereomers, then you'd say they're different. They're very, well I mean they're both different but there's this question of time scale. If I put beta D glucose into a bottle and come back, I have a mixture in water of alpha and beta D glucose. So they're different but they're not that different. They interconvert. So that's why we categorize them. And actually let me build on that a little bit. So beta D glucose has an optical rotation. Optical rotation means the amount that you rotate plain polarized light. If you've ever taken a parapolarized sunglasses and crossed the lenses, you know that when you get to a 90 degree angle light doesn't come through or if you ever have a parapolarized sunglasses and you put them over if you have an LCD watch or an LCD, maybe even the LCD screen on your phone or computer and you rotate it, you will black out because you have polarized light in many of these sorts of devices. It will go black at one angle and at a right angle it will be completely transmitting or fully transmitting of light. It's the same type of thing with sugars. They rotate that polarized light and this is one of the characteristics of optically active molecules and molecules where you have a single enantiomer and they're stereochemically active. And the degree to which glucose rotates plain polarized light is called the specific rotation and if it's used traditionally the sodium D line, that bright yellow line, if you've ever been the east coast you've seen lamps on the, you've seen lights on the highways there. Those bright yellow lights are called sodium lights. That's a 522 I believe nanometer light. Anyway, that one is often used and you rotate it by 19 degrees. Now alpha D glucose is a different stereoisomer and so it rotates plain polarized light. To a different extent the optical rotation of alpha glucose is 112 degrees. They call it specific rotation if you want to be exact in what you're calling this rather than optical rotation but optical rotation I think is a little easier to understand. Now what's cool about glucose and this comes back to your question there about why we don't consider them different molecules or we consider them different but not that different is if I go ahead and take my solution of beta D glucose with a 12 degree optical rotation, a 12 degree specific rotation and I let that solution sit. You can see the glucose inter converting from the beta isomer to the 36 to 64 mixture of beta and alpha because the rotation changes with time. It goes so upon standing we'll say both of these end up going to 53 degrees rotation, 53 degree specific rotation because the two anomers are inter converting. We call this process muto rotation. Muto is changed so basically that's a fancy way of saying changing rotation and it's going to be catalyzed by a little bit of acid or base but as I said even neutral water has acid and base in it. 10 to the negative seventh molar hydroxide, 10 to the negative seventh molar hydronium ion. So in other words the catalyst would just speed up the process. Thoughts or questions at this point? I want to talk about how we represent sugar structures and there are sort of four different notations for drawing. Is the fact that we're dealing with a flat blackboard and yet you're talking about molecules that are rich in stereochemistry and so thinking about understanding, communicating and inter relating stereochemistry is really critical when we think about sugars and their structures. So we've been drawing the chair form of beta D glucose and so I'll draw that again because we're going to start to compare and so here we go. Here's our beta D glucose and at this point I want to remind us of something. I want to remind us of where our hydrogens are. Not the hydrogens of the OH groups but the hydrogens that have been implicit in the molecule. So of course even though all of our groups on the cyclohexane ring are equatorial except if you have alpha glucose in which the alpha D glucose OH is axial we have hydrogens. So in beta D glucose we have an axial hydrogen and at the two position we have another axial hydrogen and ditto at the three position and the four position, the position that galactose had an axial hydroxy group, we have an axial hydrogen and finally at the five position as well. So in a way we have five stereogenic centers in the molecule, the stereogenic centers at positions 2, 3, 4 and 5 that are fixed, the one at position 1 that's labile and of course position 6 being a CH2OH group you have two hydrogens on the carbon it's not a chiral carbon. So there are other ways that we can represent the structure here so again I'll just write beta D glucose to remind us of the structures. I'm going to be writing for all of these. So there's another way of representing the structure that doesn't try to represent the conformation of the ring. Remember writing a cyclohexane ring, writing a six-membered ring and the conformation that I've written there is a projection. If you physically take a plastic model of cyclohexane in a chair conformation and hold it in front of a light source like an LCD projector and let the physical model project on the screen and tilt it into just the correct angle you will see all of the bonds project on the screen like this. It's still a six-membered ring but that's the projection that's why we write it that way to think about and to communicate stereochemistry. If we choose not to try to represent the shape of the molecule you can still communicate the stereochemistry. So one of the ways that people do it is just to do a flat ring and again it's sort of tilted. We're going to go ahead and use wedges to represent what's coming out of the board at us so we sort of have our ring tilted like this but we're just representing a planar structure. And now you can think about it, we can simplify things. We can write our anomeric OH up and the hydrogen down. So obviously this is a more stylized representation. It's not trying to capture the physical structure of the molecule. We can take our next position, remember we have our hydrogen down, our OH up. We can take our next position, we have our hydrogen up and our OH down. So we can represent that like this. We come to our next position now, the hydrogen's down, the OH is up. So we can represent that like this. Position four, hydrogen up, OH down and finally position five and we have hydrogen down CH2 OH up. We call this representation a Haworth projection and you'll see it used liberally in your textbook. So those two projections kind of represent the cyclic structure of the molecule and they catch all the key stereochemistry but they also require a little bit of artistry to represent and there are ways of representing the structure that may be involved less artistry. We imagine opening the structure, we imagine opening the structure to an aldehyde at this position and now we want to get all of our stereochemistry just in a zigzag structure of the molecule. So I can imagine going from one end to the other, we have six carbons and an oxygen on the end so one carbon two, three, four, five, six and let's make, let's start with the aldehyde carbon here. Remember I'm just opening the hemiasatal structure so that's going to be the aldehyde and now our chain zigs up. So in looking at the chain at this point the OH is going to be coming out at us, the hydrogen is going back so in our zigzag structure we're going to represent this as our OH coming out, our hydrogen coming back. It's important to be able to visualize these relationships and it can also be very hard to do this the first time around because you're having to train your head to really recognize three dimensionality embodied in a two dimensional drawing. Okay, our next position on the chain we've zigged down, the OH is again coming out at us and the hydrogen is coming back so we're going to represent that over here, OH, hydrogen going back. Now you almost want to continue to walk around and look at this molecule from over here like I'm doing. Now that OH is coming out and the hydrogen is going back as we come around the chain. Now we continue along here, you have to sort of position your eye from back here and say okay now that OH is going back so we sort of follow it our way, you've unwrapped the chain, you're visualizing from here that OH is going back, that hydrogen is coming out and this is just our CH2OH group. And so what I've done here in part because I'm used to seeing molecules like this is I've unwrapped the structure, drawn it in a linear fashion as the aldehyde and honestly when I think about lots and lots of stereochemistry in organic molecules the structures that I think about are linear zigzag structures like this and cyclic structures like that. What's that? The hemiasatel, yes so can I point to the hemiasatel? Is that position one? And so we just imagine this interconversion of the hemiasatel and the aldehyde. However this open form is present.003% amidst the closed form of the molecule and the closed form is a 64 to 36 ratio of the beta and the alpha anemars. Other thoughts and questions? Alright now the one that I am not in love with for a representation of molecules of sugars but that has been used traditionally to such an extent that it is absolutely integrated into almost all textbooks who discuss sugars is what's called the Fischer projection. In a Fischer projection what we're going to do is represent the molecule in a straight line and we're going to represent it so it curves backwards but we're going to show it as linear. We'll put the aldehyde group on top traditionally and now we're going to look down this way so you can sort of see alright as we do this we're going to get CHO here and then OH and H we're basically siting down this position here. I'm going to help you out with this some more in just a moment. So we're siting down this position here but the key thing in the Fischer projection is we're basically wrapping the molecule on itself. So you would have to imagine as we continue we're going to go ahead rotate about this bond 180 degrees bringing it down that's going to throw the OH pointing out pointing back on the other side. So we're going to rotate 180 degrees like so. Now that's hard to see for me the way I see this is really the relationship. I can easily see the relationship between the cyclic structure and this acyclic structure. I just sort of walk around in my mind looking at it and it helps to train yourself with models and we'll come to that in a second plastic models are the best but computer ones work. The Haworth projection is perfect for converting to the Fischer projection because the Haworth projection you say the molecules already wrapped on itself. Here's the molecule and remember that's just an aldehyde so we're going to ignore stereochemistry there. I'm going to pick that up. This OH when I pick it up is going to go off that way. This OH is going to go off that way. I take the structure I pick it up. Here was the OH I bring it vertical that OH is that way. I take the structure and here was this OH I bring it this way that one's pointing to the left. We can continue around like so and now the only point that gets confusing is over here. Let me draw how glucose is drawn first and then I'll show you how we get over there. The last position doesn't map well and I'll show you why in a second. Here's our last position. In fact for all of the D sugars they have this stereochemistry at this position at the position that's next to the terminus of it. So D at this position they didn't know it when they first started Fischer started to study the stereochemistry of the sugars but the D means this stereochemistry and it means R stereochemistry. For R and S at this position. Alright here's our Hallworth projection again. I want to show you what I see when I go ahead and do this. Let me draw this on this blackboard here. We look and we say OH OH OH OH. Now we come down to this position. Remember I picked up this ring. We're curving back on our self. We picked up this ring. It's like this. I brought it like this. So we have this high OH over here. This second OH the one at the three position here. The one at the four position over there. Now we come to the five position. If I pick this up and look at it what I have over here is now I have a carbon but I have the OH continuing down and I have a hydrogen and I have a CH2OH over here. In other words I pick this up. I look. I say how does it go? Okay well now when I pick this up that hydrogen is off to the right. The CH2OH is off to the left. The oxygen is down when I pick this up. But now you say okay how do we get from there to there. You can just imagine that you rotate about this bond. So you rotate like so, like so, like so. You move those three atoms all in a circle. You're rotating about this bond. Everything's the same until we get to the bottom position and its representation. And now we've rotated so we've rotated the OH over to here. We've rotated the hydrogen over to here. And we've rotated the CH2OH over there. And that's hard to see. It's easy to see with physical or computer models. It is hard to see in your head for the first time particularly representing seeing this representation. So this representation is the molecule, the sugar molecule wrapped around a cylinder here. It is taking that Haworth projection and wrapping it. And so one of the things that I did in trying to help you get ready to see this is I set up some stuff and we can pop our computers here at this point because I'm going to go ahead and you're welcome to play along. Johnny and Kim and I will be able to help you with this in your discussion section or in your office hours if you like. But I've set up a tool for us here on the website. And I just set it up in PyMol. So if you remember back to week three we had PyMol and we had some exercises and you downloaded PyMol onto your computer and I said well use it later. I want to use it later in the course. So now is later. So I've made some molecular models for you. And what I've done is I've started with those drawings that I just made on the blackboard. I started with the chair conformation of cyclohexane for glucose. I started with the Haworth projection. The zigzag structure that I just draw drew and the Fisher projection. And what I did for you last night was I created molecular models of each of these. So here for example is the chair conformation of beta D glucose. And remember what I talked about with the idea, whoops, let me kill the, oh I guess that is as killed as it, ah okay. That'll go a little better. How's that? Okay. Remember I talked about projections and this goes right back to our very beginnings. So there's the six-membered ring. And you go ahead and rotate it like so. Your chair emerges. I've linked, by the way I've linked Firefox in my computer so that PDBs download and open automatically in pi mole. So okay if you want to go ahead remember show can show the sticks here. And so that can show your structure in sticks. I just went to show in sticks we can get our structure. Okay I'm going to bounce back. I want to show you what I laid out for you right now. So okay so the Haworth projection should just pop up if it doesn't. Alright so there's, so I've made an unnaturally flat cyclohexane, an unnaturally flat sugar molecule and so now when you start to look, so there's our Haworth projection. Pretty much just as I've drawn it. And I'll show you a couple of other things here. I'll show you what I laid out and then I'll show you how I use these tools to think. Okay I'm going to show you the open form, the zigzag form. So there's our zigzag form that I just drew out on the blackboard for you. You can get a good look at it. You can see all your stereochemistry on there. Now the last thing I laid out for you was the Fisher projection with unnaturally flat, actually the next to the last thing I laid out was the Fisher projection. So I'm just going to move the aldehyde to the top and so that's the Fisher projection. All right so let me see if I can get our Haworth projection next to our Fisher projection. All right so remember what I said about rotating the structures. So here we go. All right so that's our anomeric carbon of the Haworth projection. That's our two carbon and you'll notice the hydrogen's off on the left, the OH is off on the right. This is our three carbon, you'll notice the OH is off on the left, the hydrogen is off on the right. We'll continue around. I'm going to rotate my Haworth projection so now we come to the four carbon and now you notice the OH is off on the right, that's the four carbon here and then I'm going to continue to rotate here and now this is the conundrum I mentioned so now we're at the five carbon and so the five carbon we have here, the hydrogen off in the cyclical area in the cyclic form, the CH2 off on the left and the oxygen that's off and you just have to imagine rotating about this bond here which is going to bring that hydrogen there, the CH2OH down and this OH here. I'll do this in the Haworth projection here like so as best as I can because of course the carbon is tetrahedral. And so there we go, now you can see our five position, the hydrogens off to the left, the OH oxygen, the oxygen that was the anomeric acetal is now off to the right. Alright, last thing I've done for you to give you some tools, see these structures, and this is what I was saying before, glucose is really an archetype of all the sugars. If you can master glucose you can master all the other sugars in your thinking and if you can understand these structures. So you have one sort of tool here, one sort of toy. Okay, the other thing I've done for you is PIMOL's native file format, PDB is sort of an interchange file format, it's also one that I've linked so my computer opens it in PIMOL when I download it in Firefox. PSE files are the native format for PIMOL so they contain all of them so I made a composite structure and I want to show you how to use this on your own. So here's a one I call glucose composite, it's just going to go to my downloads window. Alright so there's my glucose composite and I want to show you what's in here. So there's glucose in the chair form, if I click on the right here and I close the chair form there's my Haworth projection, if I click again on the open form there's the open form, if I click on the fissure projection there's the fissure projection I can just rotate it up. And so these tools or plastic models should help you visualize this stereochemistry and really, really internalize it. Now the last thing I want to do is just come back to our drawings and I just want to play off of these drawings that we had here. Okay so let's come back, this is our fissure projection of glucose. Alright, what I want to do now is to come back and show how handy these structures, these fissure projections are for visualizing other stereochemistry. Now remember we said galactose was identical to glucose except in the fore position. So now I look at galactose and I say alright I know how, if I know the glucose structure all I need to do to make galactose from the fissure projection of glucose is to change the stereochemistry at the fore position. 1, 2, 3, 4, all I do now is swap those two substituents and this structure is beta D, well I'm sorry actually technically because we're not showing the cyclic structure I should say this is D glucose and so technically this is not beta or alpha but it is regardless D galactose. Alright so the main point is we go through a lot of work to get to the fissure projections but once you're at there you can say oh I can immediately start to interrelate all my structures and we know that there are eight D sugars. There are eight D sugars because the D indicates the position at five is always fixed and we can permute the positions 2, 3 and 4 to come up with the other stereoisomers. I'm not going to bother to ask you to know them but they are allose, altrose, they have cool names, glucose, mannose, gulose, idose, galactose and tallose. So these are the eight diastereomeric D sugars. Alright well I think that wraps up what I want to say about the introduction to the structure in stereochemistry and sugars. We will pick up next time talking from the four carbon sugars on up and then move into reactions of sugars.
 All right, give yourselves a big hand.  We've done five quizzes in the class.  We've got one last one to go, which is sort of a bonus in the sense that I dropped the  lowest quiz.  We've also gone through what I consider to be some of the most intellectually challenging  material of the course.  We brought in ideas of mechanism.  We brought in ideas of synthesis.  And now we're kind of winding up the course.  And I want to cover some topics that are, I think, more interesting and in some ways  bring back some old themes and bring in some new themes as well.  So we're going to spend today, and we're going to spend Thursday talking about carbohydrates.  And carbohydrates, in one way, is a very old topic in organic chemistry.  Carbohydrate sugars are central to so much of life.  They are, of course, the sugar that you put in your coffee.  They are the glucose and fructose that make up that sugar.  They are the components of starch and cellulose.  In other words, paper on your desk and the cornstarch and so forth and potato starch in  the vegetables that you eat.  The backbone, along with phosphate, sugars, ribose, or the backbone of DNA, they're attached  to many biologically active natural products.  Sugars coat the surfaces of your cells.  Your blood types are determined by which types of sugars.  You have on the surface of your blood cells, and in turn give you antigenicity, give you  an antibody response to getting the wrong sort of blood type if you get an infusion.  So sugars are fantastically important.  We are coming back to an old theme that you learned in 51A, and that's stereochemistry.  I think the toughest thing about learning sugars isn't the stereochemistry.  It's the different representations and interrelationships.  We're going to spend some time today talking about structure and stereochemistry of sugars.  I spent last night and this morning making some special tools for you to help understand  some of the representations that are often used.  Personally, I'm a big fan of plastic models.  For the Darling models you used in 51A and maybe in some of the so-called dry labs associated  with your course, and I recommend you bring them back to learning this chapter.  Oh, no, I see tears here from the models.  You can also use your computer.  I will let you use models on the final exam, so it's useful to have them, plastic models.  So it's useful to have them complement things.  All right, I want to start with literally a simple sugar with sort of the most fundamental  or maybe the most common sugar, and we're going to draw it in a chair conformation.  The sugar that I'm drawing here is glucose.  It's kind of easy, I like it, because when I draw my chair like so, all of the substituents  are in the equatorial position, so it's very easy to remember the structure of glucose.  Now sugars have an aldehyde group, and we're going to talk more in a second, but for the  most part they exist as cyclic HMI acid towels.  I'm going to draw, we have another stereocenter for a cyclic HMI acid towel, and I'm going  to draw that hydroxy group at this position, at the one position that we'll learn is called  the anomeric position.  I'll draw it equatorial.  This molecule is called beta D glucose, and so it's a member of the class of carbohydrates  I guess if you go to the gym you might call them carbs of course, it's a nickname.  Its molecular formula is C6H12O6, and if you think about it, then the reason it gets its  name as a carbohydrate is that the formula is carbon plus H2O, and literally if I take  some sugar, if I take some table sugar, and I take sulfuric acid which is very dehydrating  and can yank all the water out and carry out a whole bunch of reactions.  If you've ever seen this done, you just put it in a beaker, pour in, put some sugar in  a beaker, pour on some consulfuric acid, and this big snake of carbon comes out of the  beaker, this big rod of frothy carbon and sulfuric acid along with a little bit of  smoke and so forth.  Anyway, I'm not going to do that demonstration here in part because it's kind of hazardous,  but it's a lot of fun.  Aldoes is a member of a class of carbohydrates, a broad, broad class of carbohydrates that  we call aldoes.  The reason we call it an aldose is that when we go ahead and unwrap the structure, when  we break up the hemisetal at the one carbon, you get an aldehyde.  There are also sugars where if you break up the hemisetal, you get a ketone, and those  are called ketosis.  We'll talk about those later.  Glucose is a six carbon sugar.  We number it from this position, one, two, three, four, five, six, and so glucose is called  an aldohexose, hex is six.  I guess to be consistent, I will write an aldose to indicate it's one of many, many.  There are a bunch of other things things get called because glucose has a six-membered  ring containing an oxygen in the closed form, in the hemisetal form.  We call it a pyranose sugar.  Pyran is a six-membered ring containing an oxygen atom.  Tetrahydropyran is a saturated six-membered ring containing an oxygen atom.  Glucose is a derivative of tetrahydropyran, so we call it a pyranose.  The other important ring containing oxygen is a five-membered ring containing an oxygen,  the aromatic compound with double bonds, and it is called furan.  If you have all hydrogens on the ring, if the ring is fully saturated, you call it tetrahydrofuran.  We've seen that THF is the solvent, and so there are other sugars that have five-membered  rings in them that you would call a furanose or a furanose form of the sugar.  And I guess as long as we're talking about names here, we would also refer to glucose  as a monosaccharide.  Glucose, of course, means one saccharide, well, sugar.  I want to give us some contrasts in structure and in stereochemistry by drawing a disaccharide  at this point, and it's going to introduce some basic concepts here.  So we're going to start with drawing another pyranose form of a ring.  We're going to have two of these linked together, so two chair cyclohexanes.  And I'm going to go ahead and draw everything the same on this ring as I did for glucose,  except at the four position, I'm going to, instead of having the hydroxy group in the  equatorial position, I'll put the hydroxy group in the axial position.  We're going to make molecule with two sugars in it.  It's one that you might have consumed this morning.  One that actually is good for you.  Well, maybe I guess all sugars are okay in moderation.  Okay, so we're going to link to another ring here.  And this ring we'll have as a glucose type ring, like so.  So here's our disaccharide.  Disaccharide is lactose.  I guess my drawing isn't the prettiest in the world.  I'm always delighted when I look at people's notebooks and see they're drawing so much  prettier than mine.  So lactose is a disaccharide.  And I think there are a couple of interesting take home messages that we get from this.  First of all, sugars can be linked together, one to the next, to the next.  Much for example is a long, long chain of sugars as is cellulose, basically a polymer  of almost infinite length.  Now you might look and say, well, it's a little different looking than glucose.  I mean, we basically formally removed one water molecule.  So if you write out the molecular formula of lactose, it's C12H2O11.  And so you'd say, well, we don't have the same ratio of carbon to hydrogen as we had  because we've connected in glucose.  But if you notice, it's still carbohydrate.  It's still effectively carbon plus H2O.  And in this case, 12 carbons plus 11 H2O's.  In the case of glucose, 6 carbons plus 6 H2O's.  So if you look at our lactose, as I said, we have two units in it.  We have our glucose unit.  And now we have another sugar unit in it.  This is a galactose unit.  So galactose, let me draw out galactose and glucose in just a second.  But I just want to make one last point.  We have a linkage from the one position of glucose, right?  So this is the one position.  And then to the four of the one position, I'm sorry, of galactose, and that's the four  position of glucose, right?  We number our way around the ring, 1, 2, 3, 4, 5, 6.  And so we call this a 1 to 4 glycosidic bond, glycosidic linkage, or glycoside bond.  I want to draw out the units, the subunits here in galactose.  So I'll draw out the two sugar units.  I'll redraw glucose again.  It pays to practice a little bit in your drawings.  And I've got to say I'm no artist as far as cyclohexane rings go.  Basically, the theory is you're going to be making parallel lines for the equatorial bond  for this OH group is parallel to the CO bond for this one.  The equatorial bond to this OH group is parallel to this one.  As I said, I'm not much of an artist, but I can get my ideas across competently.  All right, so galactose, so this is glucose, or more specifically beta-D glucose.  We'll talk about what that D means in a second.  And now we'll draw galactose, more specifically beta-D galactose.  I'll talk more about that beta in a second.  All right, so everything is the same over here except as I was indicating when I drew  our molecules, now we have a different stereochemistry at the four position.  So two isomers that have the same connectivity, all of the same atoms connected together in  the same way, but just differ in the stereochemistry of one position are diastereomers.  They're stereoisomers that are not enantiomers.  Remember when you learned about stereochemistry, you learned about enantiomers, compounds that  are non-superimposable mirror images.  You learned about diastereomers, stereoisomers that are not enantiomers, and then you learned  about constitutional isomers, molecules that have different connectivity, different arrangements  of atoms.  All right, at this point I want to draw another structure and I'm deliberately proceeding  reasonably slowly and methodically here because I think it really takes some time to bring  all these ideas into your head and to dust off the cobwebs on some of the stereochemistry  and structure that you learned back in 51A.  So I'm going to draw a different structure here.  We're going to do everything the same as glucose with one exception.  I'm going to now, instead of having our stereochemistry at the one position be equatorial instead  of having the hydroxy group at the one position be equatorial, I'm going to have our hydroxy  group at the one position be axial.  Now this is alpha D glucose and in the convention of organic chemistry you have beta as the  up position, the top face of the ring, alpha as the bottom face of the ring.  So the OH is pointing down to the bottom face as we've drawn it at what we call the anomeric  carbon.  So the carbon that makes up the hemiasatow is very, is occupies sort of a privileged position  if you think about it because unlike all the other positions your stereochemistry there  depends just on how you've closed the hemiasatow whether you've closed it so that the OH group  is equatorial or axial.  And so because of this very special diastereomeric relationship in sugar chemistry we often have  yet another word for diastereomer involving the hemiasatow to labile position so we call  it, we give it a special name as I said this is the hemiasatow position and so we call  this ananomer.  So just as we would say that beta D glucose and beta D galactose are diastereomers we  would say that alpha D glucose and beta D glucose are anomers they have a special diastereomeric  relationship to each other.  They're still diastereomers but they're a special type of diastereomer that often gets  called ananomer.  So I'll write that down.  Okay.  So most diastereomers are stereochemically stable in other words if I have a bottle of lactose  and I go away and go away for a long time and travel around the world and come back  I still have a bottle of lactose it would never become a bottle I'm sorry if I have  a bottle of galactose it would never become a bottle of glucose.  If I have an aqueous solution of galactose it is stable as galactose.  But this is not the case for anomers in which you have a hemiasatow.  We've already learned that hemiasatows are not stable compounds they are in equilibrium  with aldehydes.  Now in the case of cyclic hemiasatows we learned that they tend to favor the closed conformation.  In the case of glucose that's really, really, really strongly a preference and nevertheless  at equilibrium you have a teeny tiny bit of the aldehyde form of the open form.  In other words alpha and beta D glucose can interconvert in water and exist in equilibrium.  So I'll write this as an equilibrium I'll say in water because in the solid state the  crystal lattice keeps them stable but in water you have all sorts of chemistry occurring involving  carbonyl groups and so the alpha and beta forms of D glucose can interconvert at equilibrium  you have a 36 to 40 to 64 ratio.  And I want us to think ourselves through this interconversion process and I'm going to sketch  it out here in our mind's eye.  So I'll start with alpha D glucose.  We're not going to write a detailed mechanism.  I think by this point I'm hoping that you are on top of carbonyl chemistry enough to  be able to work through the mechanism.  Remember in the case of a cyclic hemiacetal catalyzed by acid or by base but we'll think  acid and even in water you have a little bit of acid you have 10 to the negative seventh  molar H3O plus in neutral water.  You can protonate all your oxygen atoms.  If you protonate this oxygen atom you can open the cyclic hemiacetal and so I'll write  a tautomer here.  I will write the isomer in which we've opened this linkage and so now we have our aldehyde.  Everything else is the same.  So we've just opened our linkage here to form the aldehyde.  Remember mechanistically you can think of protonate on this oxygen, push electrons down,  kick out that oxygen.  Now you have an oxocarbenium ion, take off the proton.  All right now if we imagine rotating about this bond here like so and I'm just going  to say we're talking equivalent structures here.  Generally when you rotate about a bond you don't think about a structure as being different  you think about it as being a related as just being a rotomers.  So I will rewrite rotating about the bond here like so.  So all I've done differently now is rotate about the bond to the aldehyde.  And now if you imagine closing up the structure here so we've started with alpha D glucose.  We've envisioned opening it to form the aldehyde.  At equilibrium here you have about 0.003% of the open form at equilibrium.  And now if you imagine just re-closing this  we've gone to the beta form.  We've gone from the alpha anomer to the beta anomer.  Question.  Can you do that for lactose?  Great question.  Yes and no in the linkage.  So the question is very, very good.  And I'm glad you asked it.  Okay.  Oh lactose, not, yeah lactose, right.  Absolutely very good question and I am delighted, delighted that you asked it.  So let's go back to our lactose structure.  Alright, in our lactose structure there are two types of anomeric carbons, two types  of carbons at the one position.  There's this carbon which has a hemiasatal  and then there's this carbon here which has an acetal.  Remember a hemiasatal has a hydroxy group on it.  An acetal doesn't have a hydroxy group on it.  And so the hemiasatal form absolutely can equilibrate.  And so the structure that I drew for lactose that's in your milk and whatever you drink  in the morning on your cereal, cream in your coffee, the lactose that's there, the lactose  that's in your ice cream has an equilibrating mixture of the beta and alpha anomers in the  glucose unit.  However, unless you have strong acid and by strong acid now I don't mean neutral water  or a little bit of dilute HCl but unless you have a very strong acid that can break apart  an acetal, boiling HCl solution or boiling acid, the linkage, the beta linkage off the  lactose unit is stable and doesn't undergo interconversion.  So I will write stable over here and when something interconverts we say it's labile  for this position.  Good question, good thought.  Other good questions?  Can a galactose have a carbon one like a steric shift and if so like a wool type molecule  because?  Can galactose, so the galactose unit, this subunit here at carbon one free galactose,  absolutely.  Okay, great, another great question.  So, and I want somebody to answer for me here so we saw that we had, I drew the beta compound,  what do we call this form of galactose?  Alpha.  So this is alpha D galactose and I'm going to tell you something else right now.  So it's really good to have a few pieces of core knowledge that you keep in your head  because you use those.  We've done this with, when we talked about pKa's I talked about, yeah I know the pKa  of a ketone, call it 20 whether it's a ketone or an aldehyde, know the pKa of an ester,  know the pKa of LDA.  That core knowledge is very useful because you can build on it.  There are lots and lots of different monosaccharides.  I do not, in my own head, I'm not a practicing sugar chemist, keep all of the structures  of all the different monosaccharides.  I could if I wanted to but it's just not useful for me.  But glucose and say the one diastere, one diastere or galactose are useful things to  know because it's something that you can hold on to and then you can build on it.  So when you see various other sugars, you see tallows or something, you can understand  relationships to them.  Other questions at this point?  Yeah?  Why is it that if you change the position at the one group, if you change the stereochemistry  at the one position, it's not a different sugar and if you change it at the four it  is.  The same basic idea because alpha and beta D glucose are labile because they interconvert.  We'd say they're rapidly interconverting, they're interconverting, they're the same  basic molecule.  But for ones where you have stable diastereomers, then you'd say they're different.  They're very, well I mean they're both different but there's this question of time scale.  If I put beta D glucose into a bottle and come back, I have a mixture in water of alpha  and beta D glucose.  So they're different but they're not that different.  They interconvert.  So that's why we categorize them.  And actually let me build on that a little bit.  So beta D glucose has an optical rotation.  Optical rotation means the amount that you rotate plain polarized light.  If you've ever taken a parapolarized sunglasses and crossed the lenses, you know that when  you get to a 90 degree angle light doesn't come through or if you ever have a parapolarized  sunglasses and you put them over if you have an LCD watch or an LCD, maybe even the LCD  screen on your phone or computer and you rotate it, you will black out because you have polarized  light in many of these sorts of devices.  It will go black at one angle and at a right angle it will be completely transmitting or  fully transmitting of light.  It's the same type of thing with sugars.  They rotate that polarized light and this is one of the characteristics of optically  active molecules and molecules where you have a single enantiomer and they're stereochemically  active.  And the degree to which glucose rotates plain polarized light is called the specific rotation  and if it's used traditionally the sodium D line, that bright yellow line, if you've  ever been the east coast you've seen lamps on the, you've seen lights on the highways  there.  Those bright yellow lights are called sodium lights.  That's a 522 I believe nanometer light.  Anyway, that one is often used and you rotate it by 19 degrees.  Now alpha D glucose is a different stereoisomer and so it rotates plain polarized light.  To a different extent the optical rotation of alpha glucose is 112 degrees.  They call it specific rotation if you want to be exact in what you're calling this rather  than optical rotation but optical rotation I think is a little easier to understand.  Now what's cool about glucose and this comes back to your question there about why we don't  consider them different molecules or we consider them different but not that different is if  I go ahead and take my solution of beta D glucose with a 12 degree optical rotation,  a 12 degree specific rotation and I let that solution sit.  You can see the glucose inter converting from the beta isomer to the 36 to 64 mixture of  beta and alpha because the rotation changes with time.  It goes so upon standing we'll say both of these end up going to 53 degrees rotation,  53 degree specific rotation because the two anomers are inter converting.  We call this process muto rotation.  Muto is changed so basically that's a fancy way of saying changing rotation and it's going  to be catalyzed by a little bit of acid or base but as I said even neutral water has  acid and base in it.  10 to the negative seventh molar hydroxide, 10 to the negative seventh molar hydronium  ion.  So in other words the catalyst would just speed up the process.  Thoughts or questions at this point?  I want to talk about how we represent sugar structures and there are sort of four different  notations for drawing.  Is the fact that we're dealing with a flat blackboard and yet you're talking about molecules  that are rich in stereochemistry and so thinking about understanding, communicating and inter  relating stereochemistry is really critical when we think about sugars and their structures.  So we've been drawing the chair form of beta D glucose and so I'll draw that again because  we're going to start to compare and so here we go.  Here's our beta D glucose and at this point I want to remind us of something.  I want to remind us of where our hydrogens are.  Not the hydrogens of the OH groups but the hydrogens that have been implicit in the molecule.  So of course even though all of our groups on the cyclohexane ring are equatorial except  if you have alpha glucose in which the alpha D glucose OH is axial we have hydrogens.  So in beta D glucose we have an axial hydrogen and at the two position we have another axial  hydrogen and ditto at the three position and the four position, the position that galactose  had an axial hydroxy group, we have an axial hydrogen and finally at the five position  as well.  So in a way we have five stereogenic centers in the molecule, the stereogenic centers at  positions 2, 3, 4 and 5 that are fixed, the one at position 1 that's labile and of course  position 6 being a CH2OH group you have two hydrogens on the carbon it's not a chiral  carbon.  So there are other ways that we can represent the structure here so again I'll just write  beta D glucose to remind us of the structures.  I'm going to be writing for all of these.  So there's another way of representing the structure that doesn't try to represent the  conformation of the ring.  Remember writing a cyclohexane ring, writing a six-membered ring and the conformation that  I've written there is a projection.  If you physically take a plastic model of cyclohexane in a chair conformation and hold  it in front of a light source like an LCD projector and let the physical model project  on the screen and tilt it into just the correct angle you will see all of the bonds project  on the screen like this.  It's still a six-membered ring but that's the projection that's why we write it that  way to think about and to communicate stereochemistry.  If we choose not to try to represent the shape of the molecule you can still communicate  the stereochemistry.  So one of the ways that people do it is just to do a flat ring and again it's sort of tilted.  We're going to go ahead and use wedges to represent what's coming out of the board at  us so we sort of have our ring tilted like this but we're just representing a planar  structure.  And now you can think about it, we can simplify things.  We can write our anomeric OH up and the hydrogen down.  So obviously this is a more stylized representation.  It's not trying to capture the physical structure of the molecule.  We can take our next position, remember we have our hydrogen down, our OH up.  We can take our next position, we have our hydrogen up and our OH down.  So we can represent that like this.  We come to our next position now, the hydrogen's down, the OH is up.  So we can represent that like this.  Position four, hydrogen up, OH down and finally position five and we have hydrogen down CH2  OH up.  We call this representation a Haworth projection and you'll see it used liberally in your  textbook.  So those two projections kind of represent the cyclic structure of the molecule and they  catch all the key stereochemistry but they also require a little bit of artistry to represent  and there are ways of representing the structure that may be involved less artistry.  We imagine opening the structure, we imagine opening the structure to an aldehyde at this  position and now we want to get all of our stereochemistry just in a zigzag structure  of the molecule.  So I can imagine going from one end to the other, we have six carbons and an oxygen on  the end so one carbon two, three, four, five, six and let's make, let's start with the aldehyde  carbon here.  Remember I'm just opening the hemiasatal structure so that's going to be the aldehyde and now  our chain zigs up.  So in looking at the chain at this point the OH is going to be coming out at us, the hydrogen  is going back so in our zigzag structure we're going to represent this as our OH coming out,  our hydrogen coming back.  It's important to be able to visualize these relationships and it can also be very hard  to do this the first time around because you're having to train your head to really recognize  three dimensionality embodied in a two dimensional drawing.  Okay, our next position on the chain we've zigged down, the OH is again coming out at  us and the hydrogen is coming back so we're going to represent that over here, OH, hydrogen  going back.  Now you almost want to continue to walk around and look at this molecule from over here like  I'm doing.  Now that OH is coming out and the hydrogen is going back as we come around the chain.  Now we continue along here, you have to sort of position your eye from back here and say  okay now that OH is going back so we sort of follow it our way, you've unwrapped the chain,  you're visualizing from here that OH is going back, that hydrogen is coming out and this  is just our CH2OH group.  And so what I've done here in part because I'm used to seeing molecules like this is  I've unwrapped the structure, drawn it in a linear fashion as the aldehyde and honestly  when I think about lots and lots of stereochemistry in organic molecules the structures that I  think about are linear zigzag structures like this and cyclic structures like that.  What's that?  The hemiasatel, yes so can I point to the hemiasatel?  Is that position one?  And so we just imagine this interconversion of the hemiasatel and the aldehyde.  However this open form is present.003% amidst the closed form of the molecule and the closed  form is a 64 to 36 ratio of the beta and the alpha anemars.  Other thoughts and questions?  Alright now the one that I am not in love with for a representation of molecules of  sugars but that has been used traditionally to such an extent that it is absolutely integrated  into almost all textbooks who discuss sugars is what's called the Fischer projection.  In a Fischer projection what we're going to do is represent the molecule in a straight  line and we're going to represent it so it curves backwards but we're going to show it  as linear.  We'll put the aldehyde group on top traditionally and now we're going to look down this way  so you can sort of see alright as we do this we're going to get CHO here and then OH and  H we're basically siting down this position here.  I'm going to help you out with this some more in just a moment.  So we're siting down this position here but the key thing in the Fischer projection is  we're basically wrapping the molecule on itself.  So you would have to imagine as we continue we're going to go ahead rotate about this  bond 180 degrees bringing it down that's going to throw the OH pointing out pointing back  on the other side.  So we're going to rotate 180 degrees like so.  Now that's hard to see for me the way I see this is really the relationship.  I can easily see the relationship between the cyclic structure and this acyclic structure.  I just sort of walk around in my mind looking at it and it helps to train yourself with  models and we'll come to that in a second plastic models are the best but computer ones  work.  The Haworth projection is perfect for converting to the Fischer projection because the Haworth  projection you say the molecules already wrapped on itself.  Here's the molecule and remember that's just an aldehyde so we're going to ignore stereochemistry  there.  I'm going to pick that up.  This OH when I pick it up is going to go off that way.  This OH is going to go off that way.  I take the structure I pick it up.  Here was the OH I bring it vertical that OH is that way.  I take the structure and here was this OH I bring it this way that one's pointing to  the left.  We can continue around like so and now the only point that gets confusing is over here.  Let me draw how glucose is drawn first and then I'll show you how we get over there.  The last position doesn't map well and I'll show you why in a second.  Here's our last position.  In fact for all of the D sugars they have this stereochemistry at this position at the  position that's next to the terminus of it.  So D at this position they didn't know it when they first started Fischer started to  study the stereochemistry of the sugars but the D means this stereochemistry and it means  R stereochemistry.  For R and S at this position.  Alright here's our Hallworth projection again.  I want to show you what I see when I go ahead and do this.  Let me draw this on this blackboard here.  We look and we say OH OH OH OH.  Now we come down to this position.  Remember I picked up this ring.  We're curving back on our self.  We picked up this ring.  It's like this.  I brought it like this.  So we have this high OH over here.  This second OH the one at the three position here.  The one at the four position over there.  Now we come to the five position.  If I pick this up and look at it what I have over here is now I have a carbon but I have  the OH continuing down and I have a hydrogen and I have a CH2OH over here.  In other words I pick this up.  I look.  I say how does it go?  Okay well now when I pick this up that hydrogen is off to the right.  The CH2OH is off to the left.  The oxygen is down when I pick this up.  But now you say okay how do we get from there to there.  You can just imagine that you rotate about this bond.  So you rotate like so, like so, like so.  You move those three atoms all in a circle.  You're rotating about this bond.  Everything's the same until we get to the bottom position and its representation.  And now we've rotated so we've rotated the OH over to here.  We've rotated the hydrogen over to here.  And we've rotated the CH2OH over there.  And that's hard to see.  It's easy to see with physical or computer models.  It is hard to see in your head for the first time particularly representing seeing this  representation.  So this representation is the molecule, the sugar molecule wrapped around a cylinder here.  It is taking that Haworth projection and wrapping it.  And so one of the things that I did in trying to help you get ready to see this is I set  up some stuff and we can pop our computers here at this point because I'm going to go  ahead and you're welcome to play along.  Johnny and Kim and I will be able to help you with this in your discussion section or  in your office hours if you like.  But I've set up a tool for us here on the website.  And I just set it up in PyMol.  So if you remember back to week three we had PyMol and we had some exercises and you downloaded  PyMol onto your computer and I said well use it later.  I want to use it later in the course.  So now is later.  So I've made some molecular models for you.  And what I've done is I've started with those drawings that I just made on the blackboard.  I started with the chair conformation of cyclohexane for glucose.  I started with the Haworth projection.  The zigzag structure that I just draw drew and the Fisher projection.  And what I did for you last night was I created molecular models of each of these.  So here for example is the chair conformation of beta D glucose.  And remember what I talked about with the idea, whoops, let me kill the, oh I guess that  is as killed as it, ah okay.  That'll go a little better.  How's that?  Okay.  Remember I talked about projections and this goes right back to our very beginnings.  So there's the six-membered ring.  And you go ahead and rotate it like so.  Your chair emerges.  I've linked, by the way I've linked Firefox in my computer so that PDBs download and open  automatically in pi mole.  So okay if you want to go ahead remember show can show the sticks here.  And so that can show your structure in sticks.  I just went to show in sticks we can get our structure.  Okay I'm going to bounce back.  I want to show you what I laid out for you right now.  So okay so the Haworth projection should just pop up if it doesn't.  Alright so there's, so I've made an unnaturally flat cyclohexane, an unnaturally flat sugar  molecule and so now when you start to look, so there's our Haworth projection.  Pretty much just as I've drawn it.  And I'll show you a couple of other things here.  I'll show you what I laid out and then I'll show you how I use these tools to think.  Okay I'm going to show you the open form, the zigzag form.  So there's our zigzag form that I just drew out on the blackboard for you.  You can get a good look at it.  You can see all your stereochemistry on there.  Now the last thing I laid out for you was the Fisher projection with unnaturally flat,  actually the next to the last thing I laid out was the Fisher projection.  So I'm just going to move the aldehyde to the top  and so that's the Fisher projection.  All right so let me see if I can get our Haworth projection next to our Fisher projection.  All right so remember what I said about rotating the structures.  So here we go.  All right so that's our anomeric carbon of the Haworth projection.  That's our two carbon and you'll notice the hydrogen's off on the left, the OH is off  on the right.  This is our three carbon, you'll notice the OH is off on the left, the hydrogen is off  on the right.  We'll continue around.  I'm going to rotate my Haworth projection so now we come to the four carbon and now  you notice the OH is off on the right, that's the four carbon here and then I'm going to  continue to rotate here and now this is the conundrum I mentioned so now we're at the  five carbon and so the five carbon we have here, the hydrogen off in the cyclical area  in the cyclic form, the CH2 off on the left and the oxygen that's off and you just have  to imagine rotating about this bond here which is going to bring that hydrogen there, the  CH2OH down and this OH here.  I'll do this in the Haworth projection here like so as best as I can because of course  the carbon is tetrahedral.  And so there we go, now you can see our five position, the hydrogens off to the left, the  OH oxygen, the oxygen that was the anomeric acetal is now off to the right.  Alright, last thing I've done for you to give you some tools, see these structures,  and this is what I was saying before, glucose is really an archetype of all the sugars.  If you can master glucose you can master all the other sugars in your thinking and if you  can understand these structures.  So you have one sort of tool here, one sort of toy.  Okay, the other thing I've done for you is PIMOL's native file format, PDB is sort of  an interchange file format, it's also one that I've linked so my computer opens it  in PIMOL when I download it in Firefox.  PSE files are the native format for PIMOL so they contain all of them so I made a composite  structure and I want to show you how to use this on your own.  So here's a one I call glucose composite, it's just going to go to my downloads window.  Alright so there's my glucose composite and I want to show you what's in here.  So there's glucose in the chair form, if I click on the right here and I close the chair  form there's my Haworth projection, if I click again on the open form there's the open form,  if I click on the fissure projection there's the fissure projection I can just rotate it  up.  And so these tools or plastic models should help you visualize this stereochemistry and  really, really internalize it.  Now the last thing I want to do is just come back to our drawings and I just want to play  off of these drawings that we had here.  Okay so let's come back, this is our fissure projection of glucose.  Alright, what I want to do now is to come back and show how handy these structures, these  fissure projections are for visualizing other stereochemistry.  Now remember we said galactose was identical to glucose except in the fore position.  So now I look at galactose and I say alright I know how, if I know the glucose structure  all I need to do to make galactose from the fissure projection of glucose is to change  the stereochemistry at the fore position.  1, 2, 3, 4, all I do now is swap those two substituents and this structure is beta D,  well I'm sorry actually technically because we're not showing the cyclic structure I should  say this is D glucose and so technically this is not beta or alpha but it is regardless  D galactose.  Alright so the main point is we go through a lot of work to get to the fissure projections  but once you're at there you can say oh I can immediately start to interrelate all my  structures and we know that there are eight D sugars.  There are eight D sugars because the D indicates the position at five is always fixed and we  can permute the positions 2, 3 and 4 to come up with the other stereoisomers.  I'm not going to bother to ask you to know them but they are allose, altrose, they have  cool names, glucose, mannose, gulose, idose, galactose and tallose.  So these are the eight diastereomeric D sugars.  Alright well I think that wraps up what I want to say about the introduction to the structure  in stereochemistry and sugars.  We will pick up next time talking from the four carbon sugars on up and then move into  reactions of sugars.
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