>> 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
drop 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've 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.
Carbohydrates, 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.
They're the backbone along with
phosphates, sugars, ribose,
are the back bone 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.
And I think the toughest thing
about learning sugars
isn't the stereochemistry,
it's the different
representations
and interrelationships.
And we're going to spend
some time today talking
about structure in
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.
Remember 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.
And the sugar that I'm
drawing here is glucose.
And 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 hemiacetals.
And I'm going to draw -- we
have another stereo center
for a cyclic hemiacetals.
And I'm going to draw that
hydroxy group at this position,
at the 1 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 con.
sulfuric 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.
So, glucose is a member of a
class of carbohydrates, a broad,
broad class of carbohydrates
that we call aldoses.
And the reason we call it an
aldose is that when we go ahead
and unwrap the structure, when
we break up the hemiacetal
at the 1-carbon,
you get an aldehyde.
There are also sugars
where if you break
up the hemiacetal,
you get a ketone.
And those are called ketoses.
We'll talk about those later.
Glucose is a six-carbon sugar.
We number it from this
position 1, 2, 3, 4, 5, 6.
And so glucose is
called an aldohexose.
Hex is six.
And 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 hemiacetal 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.
So 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
in it is called furan.
And if you have all
hydrogens on the ring,
if the ring is fully saturated,
you call it tetrahydrofuran
pyran -- 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.
Mono, 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 4 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.
And we're going to make a
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.
The 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 their drawings 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.
Starch, for example, is a long,
long chain of sugars
as is cellulose.
Basically a polymer of
almost infinite length.
Now, you might look at say,
well it's a little different
looking than glucose.
I mean, we've basically formally
removed one water molecule.
So if you write out
the molecular formula
of lactose, it's C12H22O11.
And so you'd say, well, we
don't have the ratio of carbon
to hydrogen as we had
because we connect in glucose.
But if you notice, it's
still a carbohydrate.
It's still effectively
carbon plus H2O,
in this case 12 carbons
plus 11 H2Os.
In the case of glucose,
6 carbons plus 6 H2Os.
So, if you look -- 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.
And 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 1
position of glucose, right?
So this is the 1 position.
And then to the 1 position
-- I'm sorry, of galactose,
and that's the 4 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 re-draw 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 4 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 stereo chemistry,
you learned about enantiomers,
compounds
that non-superimposable
mirror images.
You learned about
diastereoisomers, diastereomers,
stereoisomers that
are not enantiomers.
And then you learned about
constitutional isomers,
molecules that have
different connectivity,
different arrangements of atoms.
[ Erasing Board ]
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 1 position be equatorial,
instead of having
the hydroxy group
at the 1 position be equatorial,
I'm going to have
our hydroxy group
at the 1 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 hemiacetal is very --
it 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 hemiacetal,
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 the
diastereomer involving the
hemiacetal to labile position.
So we call it -- we
give it a special name.
As I said, this is the
hemiacetal position.
And so we call this an anomer.
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 an anomer.
And so I'll write that down.
[ Writing on Board ]
So most diastereomers are
stereochemically stable.
In other words, if I have a
bottle of lactose and I go away,
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 of --
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 hemiacetal.
We've already learned
that hemiacetals are
not stable compounds.
They are in equilibrium
with aldehydes.
Now in the case of
cyclic hemiacetals,
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.
And 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 64 ratio.
And I want us to think ourselves
through this interconversion
process.
And I'm going to sketch it
out here in our minds 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 7th
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 rotamer.
So I will rewrite rotating
about the bond here like so.
So all I've done
differently now -- woops --
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 percent
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 lactose?
>> 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.
[ Writing on Board ]
All right.
In our lactose structure
there are two types
of anomeric carbons, two types
of carbons at the 1 position.
There's this carbon,
which has a hemiacetal.
And then there's this carbon
here, which has an acetal.
Remember, a hemiacetal
has a hydroxy group on it.
An acetal doesn't have
a hydroxy group on it.
And so the hemiacetal 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
galactose 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 that galactose
have a carbon 1
on like a [inaudible] shift?
And if so, like, what would
that molecule be called?
>> Can galactose --
so the galactose unit,
this subunit here, at carbon 1.
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.
And we've done this when
we talked about pKa's.
I talked about, yeah, 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 a 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 diastereomer galactose,
are useful things to know
because it's something
that you can hold onto.
And then you can build on it.
So when you see various
other sugars, you see tallose
or something, you can understand
relationships to them.
[ Erasing Board ]
Other questions at this point?
Yeah?
[ Inaudible Audience Question ]
Why is it that if you change
the position at the 1 group --
if you change the
stereochemistry
at the 1 position it's
not a different sugar
and if you change
it at the 4 it is?
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 plane-polarized
light.
If you've ever taken a pair
of polarized 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 pair
of polarized 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.
And 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,
a molecule where you
have a single enantiomer
and they're stereochemically
active.
And the degree to which glucose
rotates plane-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
to 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
plane-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 degrees specific rotation,
and I let that solution sit,
you can see the glucose
interconverting
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 degrees specific rotation
because the two anomers
are interconverting.
We call this process
mutorotation.
Muto is change, 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
7th molar hydroxide,
10 to the negative 7th
molar hydronium ion.
So in other words, the catalyst
would just speed up the process.
[ Erasing Board ]
Thoughts or questions
at this point?
All right.
I want to talk about how we
represent sugar structures.
And there are sort of four
different notations for drawing.
I mean, the big problem we have
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 interrelating
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, at the -- 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 2 position we have another axial
hydrogen and ditto at the 3 position and the
4 position, the position that galactose had
an axial hydroxy group.
We have an axial hydrogen and finally at the
5 positoin as well.
So in a way, we have 5 stereogenic centers
in the molecule, 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 we can represent the
structure here.
Again, I’ll just write beta-D-glucose to
remind us of the structures that I’m going
to be writing for all of these.
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 6-membered ring in 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 a LCD
projector, and let the physical model project
on the screen and tilt it into just the correct
angle, you will see that all of the bonds
project on the screen like this.
It’s still a 6-membered ring but that’s
the projection, that’s why we write it that
way to think about and to communicate stereochemistry.
If we chose 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 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
is down, the OH is up, so we can represent
that like this.
Position 4—hydrogen up, OH down.
And finally, position 5 and we have hydrogen
down, CH2OH up.
We call this representation a Haworth projection
and you’ll see it used liberally in your
textbook.
So those 2 projections kind of represent the
cyclic structure of the molecule and they
catch all of the key stereochemistry but they
also require a little bit of artistry to represent.
And there are ways of representing the structure
that maybe involve less artistry.
We imagine opening the structure—if we imagine
opening the structure to an aldehyde at this
position—and now we want to get all of our
stereochemistry just in a zig zag structure
of the molecule.
So I can imagine going from one end to the
other.
We have 6 carbons and an oxygen on the end,
so 1 carbon, 2, 3, 4, 5, 6, and let’s make—lets
start with the aldehyde carbon here.
Remember, I’m just opening the hemiacetal
structure so that’s going to be the aldehyde.
And now our chain zigs up.
So, in look at the chain at this point, the
OH is going to be coming out at us, the hydrogen
is going back.
So in our zig-zag 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.
Ok, 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.
“Oh, 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
“Ok, now that OH is going back.”
So we’ve sort of followed 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 zig-zag structures
like this and cyclic structures like that.
[Student Question]
What’s that?
The hemiacetal—yes, so can I point to the
hemiacetal at position 1?
And so we just imagine this interconversion
of the hemiacetal and the aldehyde.
Remember, 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 anomers.
Other thoughts and questions?
Alright, now the one that I am not in love
with for a representation of molecules of
sugars that has been used traditionally to
such an extent that it is absolutely integrated
into almost all textbooks that discuss sugars
is what’s called the Fischer Projection.
And in a Fisher 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, where basically these sighting down
this position here.
I’m going to help you out with this some
more in just a moment.
So we’re sighting 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 and 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 the 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 see the
molecule’s 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 is pointing
to the left.
And 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.
So the last position doesn’t map well, and
I’ll show you why in a second.
So here’s our last position.
And 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, remember R and S,
at this position.
Alright, here’s our Haworth projection again
and I want to show you what I see when I go
ahead and do this.
When I go ahead and do this—I’ll draw
this on this blackboard here—so we look
and we say OH, H; OH, H; OH, H; now we come
down to this position.
Remember, I’ve picked up this ring, we’re
curving back on our self.
We’ve picked up this ring, it’s like this,
I brought it like this.
So we have this OH over here, this second
OH the one at the 3 position here, the one
at the 4 position over there.
Now we come to the 5 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?”
Ok, 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 “ok, 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 is the same until we get to the
bottom position and its representation, and
now we’ve rotated—so we rotated the OH
over to here, we rotated the hydrogen over
to here, and we rotated the CH2OH over there.
And that’s hard to see—it’s easy to
see with physical or computer models.
It’s hard to see in your head for the first
time, particularly representing—seeing this
representation.
Remember, 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 our office hours if you like.
But I 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 3, we had
PyMOL and we had some exercises and you downloaded
PyMOL to you computer and I said we’ll use
it later, I want to use it later in the course.
Ok, so now is later so I made some molecular
models for you.
And what I’ve done is I 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 zig-zag structure that I just drew, and
the Fischer projection.
And what I did for you last night is I created
molecular models for 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, I guess that’s
as killed—ah, ok.
That’ll go a little better.
How’s that?
Ok, so remember I talked about projections,
and this goes right back to our very beginnings.
So there’s the 6-membered ring.
When you go ahead and rotate it, like so,
your chair emerges.
I linked—by the way I linked Firefox in
my computer so that pdb’s download and open
automatically in PyMOL.
So, ok if you want to go ahead and remember
Show can show the sticks here, and so that
can show your structure in sticks.
I just wanted to show in sticks we can get
our structure.
Ok, we’re going to bounce back I want to
show you what I laid out for you right now.
Ok, so the Haworth projection—it should
just pop up if it doesn’t—so I made an
unnaturally flat cyclohexane, and 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.
Ok, I’m going to show you the open form,
the zig-zag form.
So there’s our zig-zag form that I just
drew out on the blackboard for you.
You can get a good look at it, you can see
all of your stereochemistry on there.
And now, the last thing that I laid out for
you was the Fischer projection with unnaturally
flat—next to the last thing I laid out was
the Fischer projections, so I’m just going
to move the aldehyde to the top.
And so that’s the Fischer projection.
Alright, so let me see if I can get our Haworth
projection next to our Fischer projection.
Alright, so remember what I said about rotating
the structures.
So, here we go.
Alright, so that’s our anomeric carbon of
the Haworth projection, that’s our 2 carbon,
and you’ll notice the hydrogen is off on
the left, the OH is off on the right.
This is our 3 carbon, you notice the OH is
off on the left, the hydrogen is off on the
right.
We’ll continue around, I’m going to rotate
the Haworth projection so now we come to the
4 carbon, and now you notice the OH is off
on the right—that’s the 4 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 5 carbon and so the
5 carbon we have here the hydrogen off 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,
this 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 5
position, our hydrogen is off to the left,
the OH oxygen—the oxygen that was the anomeric
acetal is no 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 of the sugars.
If you could master glucose, you can master
all of 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.
Ok, the other thing I’ve done for you is
PyMOLs native file format, pdb, is sort of
an interchange file format, it’s also one
that I linked so my computer opens it in PyMOL
when I download it in Firefox.
Pse files are the native format for PyMOl
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 one that I called glucose composite,
it’s just going to go into 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 Fischer projection, there’s
the Fischer 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.
Ok, so let’s come back.
This is our Fischer projection of glucose.
Alright, what I want to do now is to come
back and show how handy these structures,
these Fischer projections are for visualizing
other stereochemistry.
So remember we said galactose was identical
to glucose except in the 4 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
Fisher projection of glucose is to change
the stereochemistry at the 4 position.
1, 2, 3, 4.
All I do now is swap those 2 substituents,
and 
this structure is beta-D—sorry, 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 Fischer projections,
but once you’re at there, you can say “oh
I can immediately start to interrelate all
of my structures.”
And we know that there are 8 D sugars—there
are 8 D sugars because the D indicates the
position at 5 is always fixed, then 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 talose.
So these are the 8 diastereomeric D sugars.
Alright, well I think that wraps up what I
want to see about the introduction to the
structure and the stereochemistry of sugars.
We will pick up next time talking from the
4 carbon sugars on up and then move into reactions
of sugars
