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CLASS: Fundamentals
8-17-2011 10:00 – 11:00
DETLOFF
I.
Carbohydrates – Structures and Properties
Scribe: Tyler Rushing
Proof: Joe Vaughn
Page 1 of 7
Carbohydrate (Overview) (S2)
a. Know the Structure of glucose and ribose
a.
II.
Carbohydrates - Saccharides - Sugars (S3)
a. The word carbohydrate comes from “carbon hydrate” whose chemical constituent would be 1 carbon for every water
molecule. It is not structured like that so it is a misleading name.
b. Carbohydrates are also called saccharides.
-(audio missing from 1:19-2:02)
c. Sugars are polyhydroxy aldehydes or ketones.
d. A hydroxyl group is an -OH substituent, it’s also known as an alcohol group.
e. There are several of them on this polycarbon sugar.
f. Looking at glucose, it is drawn as a Fischer projection. It doesn’t physically look like that but it’s what the shadow of it
would look like on a 2 dimensional plane. It is a planar representation of the sugar.
g. The aldehyde group is much more reactive then the hydroxyl groups and is an important part of glucose.
-(audio missing from 2:57-3:13)
h. Glucose is an aldohexose – “aldo” refers to it having an aldehyde, “hex” meaning 6, and “ose” meaning being part of a
carbohydrate.
i. Ketohexose would mean the sugar has a ketone and it has 6 carbons.
j. An aldopentose (Ex: D-Xylose) has an aldehyde group on it and 5 carbons.
k. Tetrose would refer to a sugar with 4 carbons.
l. A ketotriose (Ex: Dihydroxyacetone) a simple ketone containing, 3 carbon sugar.
*We don’t have to memorize specific structures but should understand the prefixes and suffixes associated with these
carbohydrate groups.
III. Optical Activity – Chirality (S4)
a. There is an unusual optical property to the carbohydrates (the monosaccharides). That property is that a solution of them
can bend light. This property is found in many different chemicals and was initially discovered by Boit.
b. Turpentine, tartaric acid, and even glucose can cause a plane of polarized light to rotate.
c. This would be done by having a polarizer, a light source, and a tube filled with the solution. You can rotate a disk with a slit
in it and see where the light is coming out. The angle of the light going in would differ from the angle of the light coming
out depending on the concentration of the solution, the distance traveled, and the specific chemical property that is
bending the light.
IV. Chirality and Optical Activity (S5)
a. The way that this looks chemically is when you have a molecule with a chiral center, our example on the slide is an amino
acid held in the hand, these chemical molecules have the same chemical constituency but they are mirror images of one
another. They are said to have the opposite chirality. This is an important feature.
b. Our hands are chiral to one another. The right hand will not fit into a left glove because they are symmetrically opposed to
one another. Enzymes are the same way.
CLASS: Fundamentals
Scribe: Tyler Rushing
8-17-2011 10:00 – 11:00
Proof: Joe Vaughn
DETLOFF
Carbohydrates – Structures and Properties
Page 2 of 7
c. Chirality has a practical purpose for the cell. D isomers will not fit into the active site of an enzyme that binds L isomers. It
is like putting your right hand into a left hand glove but for an enzyme. An enzyme will not work on the wrong isomer. It
has to be of the right chirality.
d. Optical activity is how chirality is measured. Two molecules of different chirality tend to polarize light differently. It is a
way to measure that two compounds are different.
e. It is very difficult to physically separate molecules that are mirror images of each other but you can tell they are mirror
images of each other by measuring optical activity.
V. Carbohydrates - Saccharides - Sugars (S6)
a. When you look at a carbohydrate (glucose as an example on the slide), all of the carbons except the first and last carbons
can be different chiral centers (the red starred ones). If you alter where the hydroxyl group is, it has a different chirality and
is therefore a different molecule. It has the same chemical constituents, but if this hydroxyl group is drawn on the other
side of the Fischer projection, it would be named differently.
b. Glucose has 4 chiral centers.
VI. Generic Formulas and Fischer projections (S7)
a. The Fischer projection is just making everything planar.
b. Glyceraldehyde (ex. on the slide) is a very simple and small molecule with 1 chiral center.
c. If the substituents attached to the chiral center are coming out of the plane towards you, you use the black triangles to
represent this. If the substituents attached to the chiral center are going in towards the plane you use the black dots.
d. You can see that L-Glyceraldehyde and D-Glyceraldehyde are mirror images of one another, and you can draw them by
putting the hydroxyl group on the other side of the Fischer projection.
VII. Absolute Configurations of Sugars (S8)
a. There are two different forms of glucose, L-Glucose and D-Glucose. They are mirror images of one another.
b. The difference between these two forms of glucose is based on farthest chiral carbon from the aldehyde (indicated with an
asterisk). On a Fischer projection you could tell the difference between a D or L carbohydrate just by comparing it to the
smallest carbohydrate with a chiral center (D-Glyceraldehyde). D-Glyceraldehyde has the hydroxyl group on the right hand
side and L-Glyceraldehyde would have it on the left hand side. This carbon is called the reference carbon. It’s solely there
so we can come up with these different names (e.g. D and L).
VIII. Enantiomers and Diastereomers (S9)
a. If you create a mirror image by flipping the hydroxyl group on the reference carbon, these two molecules would be called
enantiomers. Enantiomers are mirror images.
b. If you flip several hydroxyl groups and haven’t changed the chemical constituency but just the stereo properties and how
they are attached, then they become diastereomers of one another. They are not mirror images of one another.
IX. Racemic Mixtures (S10)
a. Looking at mannose, it is just a diastereomer of glucose. It is almost a mirror image of D-Glucose but it differs at the second
chiral center as well. The mirror image of L-Mannose is D-Mannose, just by convention.
b. A racemic mixture is a mixture of two enantiomers. This can occur chemically in equal proportions. If a chemical just
interacts with a particular molecule, it can create a situation where there is a racemic mixture.
c. It would be very difficult to chemically separate a racemic mixture of two enantiomers.
d. They can be separated by derivatizing that substance with a chiral reagent and converting the components to a mixture of
diastereomers.
e. Diastereomers can be separated more easily from one another. They can be separated and then the original compounds
can be regenerated.
X.
Resolution of Racemic Mixture (S11)
a. Louis Pasteur was the first person to separate out the two enantiomers of a racemic mixture. (He used tartaric acid)
b. The enantiomers formed two distinctly different (and opposite) crystals and so he was able to separate them out with
tweezers based on how the crystals looked. He could then mix them back together in equal amounts and reform a racemic
mixture.
CLASS: Fundamentals
Scribe: Tyler Rushing
8-17-2011 10:00 – 11:00
Proof: Joe Vaughn
DETLOFF
Carbohydrates – Structures and Properties
Page 3 of 7
c. Each enantiomer had different stereo properties and would twist light to different degrees. The racemic mixture would
twist light to an intermediate degree.
XI. Aldose Tree (S12)
a. Looking at the aldehyde versions of these carbohydrates, glucose is a diastereomer of all the other aldohexoses at the
bottom of the tree. The reference carbon is the carbon shown in grey (Carbon 5).
b. The majority of these carbohydrates are found in nature as the D form.
c. The enzymes in nature tend to favor the construction of the D form. There are some L forms but they are rare. It is thought
that this just happened and that the enzymes were able to recognize the D form much more readily than the L form.
d. In amino acids, it is exactly the opposite and the L form dominates.
e. All of the different diastereomers will have different names and by convention there are L forms of those, which are the
mirror images.
f. Addition of 1 hydroxylated carbon to a sugar makes a new compound. This is how the tree is arranged. Hydroxylated
carbons are added as you move down the tree.
g. D-Glucose and D-Galactose are not mirror images of one another but they are epimers because they differ at 1 chiral center
(the hydroxyl group is on the other side).
XII. Absolute Configurations of Sugars (S13)
a. When the polarized light, stereo-isomeric contraption described earlier is used, a solution such as glucose can be put in and
one can see whether it will be dextrorotatory, which is in the clockwise direction (+) or levorotatory, which is in the
counterclockwise direction (-).
b. Compounds are all different in this respect.
c. When we use D and L designations, they do not signify whether something will be dextrorotatory or levorotatory. It’s
simply a designation of which side the hydroxyl group is on in respect to the reference carbon. You would use (+) or (-) to
designate dextrorotatory or levorotatory respectively.
XIII. Ketose Tree (S14)
a. A ketotriose is the simplest ketose.
b. The first chiral center that appears is the third carbon on a ketotetrose. This gives you the designation of whether it is a D
or L, because it’s the furthest chiral carbon from the aldehyde.
c. Ribulose is like ribose except it has a ketone instead of an aldehyde.
d. D or L is still designated at the reference carbon like aldoses
XIV. Epimerization (S15)
a.
The ketose and aldose group can be interconverted by what’s called tautomerization. This can occur under highly alkaline
conditions.
b. D-Mannose can be converted to D-Glucose this way. The hydroxyl group is flipped to the other side of the Fischer projection.
Everything else is identical between the epimers D-Mannose and D-Glucose. Again, epimers are different only at one chiral
center (C-2 epimer of D-Glucose is D-Mannose).
c. The keto group can also form, converting D-Mannose into D-Fructose.
d. Conversion of Glucose to Fructose is at a very low rate in physiological conditions and requires enzymes.
XV. Oxidation (S16)
a. The aldehyde and ketone’s of aldoses and ketoses are much more reactive than the hydroxyl groups.
b. An aldehyde group can be oxidized to a carboxylic acid group (via Br2 in H2O).
c. You can actually oxidize keto groups as well if using an alkaline solution with silver or copper.
XVI. Oxidation (S17)
a. An aldaric acid can be formed from and aldehyde group if a very strong oxidizing agent is used (Ex: HNO3).
b. An aldaric acid oxidizes not only the aldehyde group but the hydroxyl attached to the end carbon so you have two
carboxylic acid groups.
XVII.
a.
Reduction (S18)
The aldehyde group can also be reduced creating an alditol (via sodium borohydride (NaBH4)).
CLASS: Fundamentals
Scribe: Tyler Rushing
8-17-2011 10:00 – 11:00
Proof: Joe Vaughn
DETLOFF
Carbohydrates – Structures and Properties
Page 4 of 7
b. Alditols are used in foods that aren’t supposed to produce a lot of glucose in the bloodstream. These are reduced
carbohydrates that have had the aldehyde groups turned into a hydroxyl group (Ex: Sorbitol).
c. If a ketone group is reduced, it forms a racemic mixture where the hydroxyl is either on one side or the other, wherever the
ketone group used to be.
XVIII.
a.
b.
c.
Hemiacetal (S19)
There is one reaction that goes on spontaneously and it cyclizes these monosaccharaides.
Monosaccharides are usually in cyclic form in the body. Only about 1% are in these linear forms and that’s actually in
equilibrium with the cyclic form.
Cyclization takes place with one of the alcohol groups on the carbohydrate interacting with the aldehyde group, which
creates a hemiacetal group.
XIX. Aldose Cyclization (S20)
a. This slide shows what that cyclization looks like. Cyclization of D-Glucose forms a six atom ring which is called a pyran. So
the name would be changed to glucopyranose.
b. Normally you have 4 chiral centers. The aldehyde carbon always looks the same stereo isometrically until it cyclizes. It is
called the anomeric carbon.
c. This is a reversible reaction so the carbohydrate can cyclize and uncyclize every once and a while.
d. Ultimately there are two different forms. One with the anomeric hydroxyl group above the ring (beta) and one with the
hydroxyl group below the ring (alpha).
e. These two forms are distinct from each other stereo isometrically, and enzymes view them differently. These 2 forms are
called anomers of one another.
f. How this anomeric carbon forms linkages with other groups is very important. This creates the difference between
cellulose and glycogen for example (you can digest 1 but not the other).
g. Haworth came up with these more three dimensional structures called Haworth structures.
XX. Fehlings Reaction for Aldehydes (S21)
a. The aldehyde group, which is reversible with the pyranose form, is reactive and can reduce other agents inside a test tube.
Its One way you can tell how much glucose or aldehyde is in a sample.
b. All that you need to do is heat it in an alkaline solution with Fehlings reagent that has copper in it (starts as a blue solution).
This copper then becomes reduced and forms a reddish precipitate.
c. Since the copper is reduced, the carbohydrate is oxidized and a carboxylic acid group will be formed.
XXI. Fischer Projection Formulas (S22)
a. When drawing a Fischer projection of an alpha vs beta anomer, you can see that the alpha anomer has the hydroxyl at C-1
tucked under the ring.
b. The beta anomer has the hydroxyl at C-1 outside or above the ring.
c. Remember, C-4 is the reference carbon which tells you whether it is D or L.
*Won’t be asked what is an alpha or a beta anomer but know that there are two different forms and that they are
chemically distinct and enzymatically distinct and have different properties*
XXII.
Hemiketal (S23)
a. With a ketone group, an alcohol group on the carbohydrate can attack the ketone and form what is called a hemiketal.
XXIII.
Ketose Cyclization (S24)
a. This (referring to hemitketal formation) is how a ketose like fructose would cyclize.
b. If a carbohydrate forms a 5 carbon ring, it looks like a furan ring. Therefore, these are called furanoses.
c. Furanoses also have a chiral anomeric carbon.
d. Just as with pyranoses, if the hydroxyl on the anomeric carbon is up it is a beta furanose and if the hydroxyl group is down it is
an alpha furanose.
XXIV.
Ketose Fischer Projection (S25)
CLASS: Fundamentals
Scribe: Tyler Rushing
8-17-2011 10:00 – 11:00
Proof: Joe Vaughn
DETLOFF
Carbohydrates – Structures and Properties
Page 5 of 7
a. There are also Fischer projections for furanoses where if the hydroxyl on C-2 is tucked under the ring it is alpha and if the
hydroxyl is outside or above the ring it is beta.
XXV.
a.
b.
c.
Cyclization (S27)
The hydroxyl groups should be chemically equivalent, they should be able to attack the aldehyde group in glucose equally.
However, ring stability dictates which hydroxyl will successfully attack the aldehyde or ketone.
Seven carbon rings are highly unstable and four carbon rings have too much strain as well.
Only stable ones are the ones that lead to the pyranose form (6 membered ring) and furanose form (5 carbon ring).
XXVI.
a.
Anomeric Configurations (S28)
The different anomeric configurations (alpha and beta) would bend light to a different degree in a polarizer so they have
different stereo properties.
*He said not to worry about the stuff on Slide 29 (deciding if its alpha or beta)
XXVII.
a.
b.
c.
d.
e.
Mutarotation (S30)
If you left a-D-Glucopyranose in a solution in a polarizer, it would bend light differently over time, because the alpha and
beta anomers come into equilibrium with each other in solution.
It does this by having a linear intermediate.
Cyclization is heavily favored but every once and a while it can uncyclize and you can have recyclization into the different
opposite anomer.
In this example it would tend to favor B-D-Glucopyranose at about 63.6%. The rest as a-D-Glucopyranose and a trace
amount in the linear form.
alpha-D-Glucopyranose would bend the polarized light 112 degrees while Beta-D-Glucopyranose would only bend it 19
degrees, but the mixture would ultimately bend light at an intermediate amount; in this case it would be 52.5 degrees.
These (+) values mean that it is bending light dextrorotatory.
XXVIII. Conformations of Cyclic Sugars (S31)
a. We lose some of the structural information in the Haworth projections. It can be in the six ring forms such as a-DGlucopyranose.
b. Hydroxyls are placed out in equatorial positions (shown in slide).
c. When substituents are placed axially, they tend to interfere with each other sterically. So, the actual form favors placing all
of the substituents in the equatorial positions.
d. Glucose has more equatorial substituents than the other aldohexoses, which may be why it is such a predominate
monosaccharide. It forms these chair structures that are more sterically stable.
e. Possible ring conformations formed from monosaccharide include chairs, boats, skews, half chairs, and envelopes. They all
exist but the chair structure tends to be favored.
XXIX.
a.
b.
c.
d.
XXX.
a.
b.
XXXI.
a.
Major Sugar Residues of Mammalian Glycoconjugates (S33)
There are several different sugar residues. Think of residues as an independent unit in a polymer. A monosaccharide is an
independent unit in a polysaccharide.
There are different sugars such as glucose, mannose, fucose, galactose, xylose.
There are amine groups that are put on sometimes to give glycosoamines.
All of these have some biological relevance.
Common Alditols (S35)
As mentioned before, the aldehyde group can be reduced. There are several different compounds that are the reduction
products of this carbohydrate reduction.
A lot of these are artificial sweeteners like sorbitol, which is an alditol (aldehyde has been reduced to a hydroxyl group).
Muramic Acid (S37)
Muramic acid has an amino group and another constituent on it. Muramic acid is a component of bacterial cell walls.
CLASS: Fundamentals
Scribe: Tyler Rushing
8-17-2011 10:00 – 11:00
Proof: Joe Vaughn
DETLOFF
Carbohydrates – Structures and Properties
Page 6 of 7
XXXII. Sialic Acid (38)
a. Sialic acids are used for receptor interactions.
b. Laetrile (on slide 39) is also a monosaccharide and has been claimed in the past to cure cancer, but there is no evidence for
this.
(End – 44:18)