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Carbohydrates
Chapter 25
25-1
Carbohydrates
 Carbohydrate:
A polyhydroxyaldehyde, a
polyhydroxyketone, or a compound that gives
either of these compounds after hydrolysis.
 Monosaccharide: A carbohydrate that cannot be
hydrolyzed to a simpler carbohydrate.
• They have the general formula CnH2nOn, where n varies
from 3 to 8.
• Aldose: a monosaccharide containing an aldehyde
group.
• Ketose: a monosaccharide containing a ketone group.
25-2
Importance of Carbohydrates to us….
polymerize
CO2
+
H2O
photosynthesis
glucose
clothing fiber
wood
cellulose
giving structure
to plants
polymerize
chlorophyll
light
starch, plant seeds
eaten by animals
CO2
+
H2O
+
energy
glucose
glycogen (liver)
25-3
Monosaccharides
 Monosaccharides
are classified by their number
of carbon atoms:
N ame
Trios e
Tetros e
Pen tos e
Hexose
Heptose
Octose
Formula
C3 H6 O3
C4 H8 O4
C5 H1 0 O5
C6 H1 2 O6
C7 H1 4 O7
C8 H1 6 O8
25-4
Monosaccharides
 There
are only two trioses:
Chiral Center
R and S
stereoisomers
CHO
CH2 OH
CHOH
C= O
CH2 OH
Glyceraldehyde
(an aldotriose)
CH2 OH
D ihydroxyacetone
(a ketotriose)
 These
compounds are referred to simply as
trioses, tetroses, and so forth tellling the number
of carbon atoms present.
25-5
Review Fischer Projections
 Fischer
projection: A two dimensional
representation for showing the configuration of
carbohydrates.
• Horizontal lines represent bonds projecting forward.
• Vertical lines represent bonds projecting to the rear.
• The more highly oxidized carbon is shown at the top.
CHO
H
C
OH
convert to a
Fisch er p rojection
CH2 OH
(R)-Glycerald ehyde
(three-dimensional
represen tation )
CHO
H
OH
CH2 OH
(R)-Glyceraldeh yd e
(Fis cher projection)
.
25-6
D,L Monosaccharides
 In
1891, Emil Fischer made the arbitrary
assignments of D- and L- to the enantiomers of
glyceraldehyde.
CHO
H
OH
CH2 OH
D -Glyceraldehyde
(R)-Glyceraldehyde
[]D25 = +13.5
CHO
HO
H
CH2 OH
L-Glyceraldehyde
(S)-Glyceraldehyde
[]D25 = -13.5
25-7
D,L Monosaccharides
 According
to the conventions proposed by
Fischer:
• D-monosaccharide: A monosaccharide that has the
same configuration at its penultimate (next to bottom)
carbon as D-glyceraldehyde; that is, its -OH is on the
right when written as a Fischer projection.
• L-monosaccharide: A monosaccharide that has the
same configuration at its penultimate carbon as Lglyceraldehyde; that is, its -OH is on the left when
written as a Fischer projection.
25-8
D,L Monosaccharides
 D-aldotetroses
and the two most abundant Daldopentoses in the biological world:
CHO
CHO
H
OH
HO
H
OH
H
CH2 OH
D-Erythrose
CHO
CHO
H
OH
H
H
H
H
OH
H
OH
OH
H
OH
H
OH
CH2 OH
D-Threose
D-aldotetroses
Expect four stereoisomer
22 for aldotetroses. Two D
and two L.
CH2 OH
D-Ribose
CH2 OH
2-Deoxy-Dribose
D-aldopentoses
Expect total of 8 (=23)
steroisomers. Four D,
25-9
four L.
D,L Monosaccharides
 The
most abundant hexoses:
CHO
H
OH
HO
H
H
OH
H
OH
CH2 OH
D-Glu co s e
CHO
H
OH
HO
H
HO
H
H
OH
CH2 OH
D -Gala cto s e
aldohexoses
Expect 16 stereoisomers 24 for
aldohexoses. Eight D and
eight L.
CH2 OH
C O
HO
H
H
OH
H
OH
CH2 OH
D -Fru cto s e
ketohexose
Expect 8 stereoisomers 24
for ketohexoses. Four D
and four L.
25-10
D Aldohexoses binary display
All
altruists
gladly
make gum
in gallon
tanks.
0= 000
1=001
2=010
3=011
L.Fieser
4=100
5=101
6=110
7=111
There is
also the L
series,
the mirror
image
structures
25-11
Amino Sugars
 Amino
sugar: A sugar that contains an -NH2
group in place of an -OH group.
• Only three amino sugars are common in nature
• N-Acetyl-D-glucosamine is a derivative of Dglucosamine.
H
HO
H
H
CHO
NH2
H
OH
OH
CH2 OH
CHO
H2 N 2 H
HO
H
H
OH
H
OH
CH2 OH
CHO
H
NH2
HO
H
HO 4 H
H
OH
CH2 OH
D -Glu cosamine D -Mannosamine D -Galactosamine
H
HO
H
H
CHO O
NHCCH3
H
OH
OH
CH2 OH
N-Acetyl-D glucos amin e
25-12
Physical Properties
 Monosaccharides
are colorless crystalline solids,
very soluble in water, but only slightly soluble in
ethanol.
• sweetness relative to sucrose:
Carbohydrate
S w eetness
Relative to
S ucrose
Fructos e
In vert su gar
Sucrose (tab le sugar)
Hon ey
Glucose
Maltos e
Galactose
Lactose (milk s ugar)
1.74
1.25
1.00
0.97
0.74
0.33
0.32
0.16
Artificial
Sw eetener
Saccharin
Aces ulfame-K
Asp artame
S w eetness
Relative to
S ucrose
450
200
160
25-13
Cyclic Structure
 Monosaccharides
have hydroxyl and carbonyl
groups in the same molecule and those with five
or more carbons exist almost entirely as five- and
six-membered cyclic hemiacetals.
• Anomeric carbon: The new stereocenter created as a
result of cyclic hemiacetal formation.
• Anomers: Carbohydrates that differ in configuration at
their anomeric carbons named  and b.
25-14
Haworth Projections
 Haworth
projections
• Five- and six-membered hemiacetals are represented
as planar pentagons or hexagons viewed through the
edge.
• They are commonly written with the anomeric carbon
on the right and the hemiacetal oxygen to the back
right.
• The designation b- means that the -OH on the
anomeric carbon is cis to the terminal -CH2OH;
- means that it is trans to the terminal -CH2OH.
25-15
Haworth Projections
1
CHO
OH
H
HO
top
H
H
OH
H 5 OH
CH2 OH
D -Glucose
red raw to sh ow th e -OH
on carbon-5 close to the
aldeh yd e on carbon-1
Lay molecule
on side.
cis, b
CH2 OH
OH
H5
O
H
OH H C
1 H
HO
H
anomeric
carbon
CH2 OH
O OH(b)
H
H
OH H
HO
H
H OH
b-D -Glucopyranose
(b-D -Glucose)
OH
trans, 
anomeric
carb on
CH2 OH
O
H
H
H
+
OH H
HO
OH()
H OH
-D -Glucopyranose
( -D -Glucos e )
25-16
Haworth Projections
• Six-membered hemiacetal rings are shown by the infix
-pyran-.
• Five-membered hemiacetal rings are shown by the
infix -furan-.
O
O
Furan
Pyran
25-17
Conformational Formulas
• Five-membered rings are so close to being planar that
Haworth projections are adequate to represent
furanoses.
HOCH2
H
H
O
H
OH ( )
OH
OH
-D -Rib ofuranose
(-D -Ribose)
H
HOCH2
H
H
OH ( b)
O
H
H
OH
H
b-2-D eoxy-D -ribofu ran os e
(b-2-D eoxy-D -ribose)
25-18
Conformational Formulas
• Other monosaccharides also form five-membered
cyclic hemiacetals.
• Here are the five-membered cyclic hemiacetals of Dfructose, a ketohexose.
1
1
HOCH2
5
O
H HO
H
HO
CH2 OH
2
CH2 OH
2
OH( )
H
 -D -Fructofuranose
( - D -Fructos e)
C=O
HO
H
4
H
OH
5
H
OH
3
6
CH2 OH
D -Fru ctose
HOCH2
5
O
H HO
H
OH ( b)
2
CH2 OH
HO
H
1
b - D -Fru ctofu ran os e
(b- D -Fructose)
25-19
Conformational Formulas; b to  conversion
• For pyranoses, the six-membered ring is more
accurately represented as a chair conformation.
H OH
H
H O
HO
HO
H
H
OH
H
OH
H OH
HO
OH
HO
H
H
O
OH
Open chain
form
H
b-D -Glu copyran os e
(b-D -Glucos e)
rotate about
C-1 to C-2 bond
H OH
H
H OH
HO
HO
H
H
OH
H
O
OH
H O
HO
HO
H
H
H
OH
OH
-D -Glucop yranose
(-D -Glu cose)
25-22
Conformational Formulas
• The orientations of groups on carbons 1-5 in the
Haworth and chair projections of b-D-glucopyranose
are up-down-up-down-up.
6 CH OH
2
H
4
5
H
OH
HO
3
H
O
6
1
H
H
2
OH
b-D -Glucopyranose
(Haw orth projection)
CH2 OH
4
OH(b)
O
HO
HO
5
3
OH( b)
2
OH 1
b-D -Glu copyran os e
(chair conformation )
25-23
Mutarotation
 Mutarotation:
The change in specific rotation that
occurs when an  or b form of a carbohydrate is
converted to an equilibrium mixture of the two.
[]
Mon os accharide
[] after
% Present at
Mutarotation Equ ilib riu m
-D -glu cose
b-D -glucos e
+112.0
+18.7
+52.7
+52.7
36
-D -galactos e
b-D -galactose
+150.7
+52.8
+80.2
28
72
HO
HO
CH2 OH
O
OH
b-D -Glu cop yranose
[] D2 5 +18.7
OH ( b)
64
+80.2
HO
HO
CH2 OH
O
HO
OH ( )
-D -Glucopyranose
25-24
[] D 25 +112
Hemiacetals and Acetals, carbonyls and alcohols
Addition
reaction
.
Substitution reaction
(Unstable
in Acid;
Unstable in
base)
(Unstable
in Acid;
Stable in
base)
25-25
Glycosides, anomeric OH becomes OR, acetal formation.
 Glycoside:
A carbohydrate in which the -OH of
the anomeric carbon is replaced by -OR.
• methyl b-D-glucopyranoside (methyl b-D-glucoside)
glycos idic
bond
CH2 OH
CH2 OH
CH2 OH
O OH
OH
O OCH3
H
H
+
H
H
H
H
H
+
CH
OH
+
OH H
3
OH H
OH H
-H
O
2
HO
H
HO
OCH3
H
HO
H OH
H OH
H OH
b-D -Glu copyran os e
Methyl b-D -glu coMeth yl -D -glu co(b-D -Glu cose)
pyran os ide
p yranosid e
( Methyl b-D -glucos ide) (Methyl -D -glucos ide)
25-26
Glycosides, acetals
 Glycosidic
bond: The bond from the anomeric
carbon of the glycoside to an -OR group.
 Glycosides are named by listing the name of the
alkyl or aryl group bonded to oxygen followed by
the name of the carbohydrate with the ending -e
replaced by -ide.
• methyl b-D-glucopyranoside
• methyl -D-ribofuranoside
25-27
N-Glycosides
 The
anomeric carbon of a cyclic hemiacetal also
undergoes reaction with the N-H group of an
amine to form an N-glycoside.
• N-glycosides of the following purine and pyrimidine
bases are structural units of nucleic acids.
O
NH2
HN
O
N
H
U racil
N
O
N
H
Cytosine
O
HN
O
NH2
CH3
N
H
Thymine
O
N
N
N
H
Ad enin e
N
N
HN
H2 N
N
N
H
Guan ine
25-28
N-Glycosides
• The b-N-glycoside formed between D-ribofuranose and
cytosine.
NH2
N
O
HOCH2
O
H
H
N
a b-N -glycosid ic
bond
H
H
HO
OH
anomeric
carbon
25-29
Reactions
25-30
Reduction to Alditols, aldehyde  alcohol
 The
carbonyl group of a monosaccharide can be
reduced to an hydroxyl group by a variety of
reducing agents, including NaBH4 and H2/M.
HO
HO
CH2 OH
O
OH
OH
b-D -Glucop yranose
CHO
H OH
HO H
H OH
H OH
CH2 OH
D -Glu cose
NaBH4
CH2 OH
H OH
HO H
H OH
H OH
CH2 OH
D -Glucitol
(D -Sorbitol)
An
alditol
25-31
Other alditols
• Other alditols common in the biological world are:
CH2 OH
H
OH
H
OH
CH2 OH
Eryth ritol
CH2 OH
HO
H
HO
H
H
OH
H
OH
CH2 OH
D -Mann itol
CH 2 OH
H
OH
HO
H
H
OH
CH 2 OH
Xylitol
25-32
Oxidations
Oxidation can be done in several ways.
Tollens reagent (Ag+(NH3)2 or Benedict’s solution
(Cu2+ tartrate complex). Not synthetically useful
due to side reactions.
Bromine water oxidizes aldoses (not ketoses) to
monocarboxylic acids (Aldonic Acids).
Nitric Acid oxidizes aldoses to dicarboxylic acids
(Aldaric acids).
Enzyme catalyzed oxidation of terminal OH to
carboxylic acid (Uronic Acid)
Periodic Acid oxidizes and breaks C C bonds.
Later for that.
25-33
Reducing Sugars
 Sugars
with aldehyde (or ketone group) in
solution. The group can be oxidized and is
detected with Tollens or Benedicts solution.
Ketone groups converted to aldehyde via
tautomeric shifts (later).
25-34
Problem with Tollens
 2-Ketoses
are also oxidized to aldonic acids in
basic solution (Tollens).
CH2 OH
(1)
C= O
( CHOH ) n
CH2 OH
A 2-ketose
CHOH
C-OH
(2)
( CHOH ) n
CH2 OH
An enediol
CHO
CHOH
(3)
( CHOH ) n
CH2 OH
An aldos e
Ketose to aldose conversion
via keto enol tautomerism
COOH
CHOH
( CHOH ) n
CH2 OH
An aldonic acid
Oxidation
Reducing sugar
25-35
Oxidation to carboxylic acids
25-37
Oxidation to Uronic Acids
 Enzyme-catalyzed
oxidation of the terminal -OH
group gives a -COOH group.
CHO
H
OH enzyme-catalyzed
oxidation
HO
H
H
OH
H
OH
CH2 OH
D -Glucose
H
HO
H
H
CHO
OH
COOH
O
H
HO
OH
HO
OH
OH
COOH
D -Glucuronic acid
(a uronic acid)
OH
25-38
Oxidation by periodic acid, HIO4 or H5IO6
 Periodic
acid cleaves the C-C bond of a glycol.
OH
C OH
O - 2 H2 O
+
I
OH
C OH HO
OH
HO
A 1,2-diol
Periodic acid
OH
O
I
OH
C O
OH
C O
C O
C O
+ H3 IO 4
Iodic acid
A cyclic periodic
ester
25-40
Oxidation by HIO4
• It also cleaves -hydroxyketones
H
H
H
H C OH
C O
+ H2 O
H C OH
H5 IO 6
HO C OH
R
R
-Hydroxyketone
H C
O
HO C
O
R
Hydrated
in termediate
• and -hydroxyaldehydes.
O
H C
H C OH
OH
+ H2 O
R
-Hydroxyald ehyde
H C OH
H C OH
R
Hydrated
in termediate
H5 IO6
OH
H C O
H C O
R
25-41
Examples. Identify each of the glucose derivatives.
A + 4 HIO4 yielded 3 HCO2H + HCHO + OHC-CO2H
B + 5 HIO4 yielded 4 HCO2H + 2 HCHO
C + 3 HIO4 yielded 2 HCO2H + 2 OHC-CO2H
Analysis of A:
4 moles of periodic acid used. 4 bonds
broken.
Products:
Formic acid from –CHOH- or CHO-.
Formaldehyde from CH2OHOHC-CO2H from –CHOH-CO2H
H
HO
CO2H
OH
H
H
OH
H
OH
25-42
CH2OH
Another example
of methyl b-D-glucoside consumes two
moles of HIO4 and produces one mole of formic
acid, which indicates three adjacent C-OH
groups.
 Oxidation
periodic acid cleavage
at thes e tw o b on ds
H
HO
HO
CH2 OH
O
2 HIO
4
2 HIO
OCH3
OH
Meth yl b-D -glucopyranoside
O
5
O
C CH2 OHO
OH O
C
C
OCH3
H
H
25-43
Osazones, Epimers
O
CHO
CHOH
3 PhNHNH2
CH=NNHPh
PhCHO
C=NNHPh
O
aldose
osazone
osone
25-44
Use of osazone in structure determination
Fischer found that (+) glucose and (+) mannose yielded the
same osazone indicating that they differed only at the C2
configuration. Hence, if we know the configuration of (+)
glucose we immediately have that of (+) mannose.
Stereoisomers that differ in configuration at only one
stereogenic center are called epimers. D-glucose and Dmannose are epimers.
NNHPH
CHO
H
HO
CHO
HC
OH
H
PhHNN
HO
H
H
OH
H
OH
H
OH
H
OH
CH2OH
D glucose
CH2OH
HO
H
HO
H
H
OH
H
OH
CH2OH
D mannose
25-45
Glucose Assay: diabetes (background)
 The
analytical procedure most often performed in
the clinical chemistry laboratory is the
determination of glucose in blood, urine, or other
biological fluid.
25-46
Glucose Assay
 The
glucose oxidase method is completely
specific for D-glucose.
25-47
Glucose Assay
• The enzyme glucose oxidase is specific for b-Dglucose.
• Molecular oxygen, O2, used in this reaction is reduced
to hydrogen peroxide H2O2.
• The concentration of H2O2 is determined
experimentally, and is proportional to the
concentration of glucose in the sample.
• In one procedure, the hydrogen peroxide oxidizes otoluidine to a colored product, whose concentration is
determined spectrophotometrically.
25-48
Killani-Fischer lengthening of chain
As lactones
Get both epimers.
25-49
Ruff Degradation shortening of chain
25-50
Fischer proof of structure of glucose
Emil Fischer received the 1902 Nobel prize for
determining the structure of glucose.
What was available to him in 1888?
•Theory of stereoisomerism
•Ruff degradation
•Oxidation to aldonic and aldaric acids
•Killani-Fischer synthesis
•Various aldohexoses and aldopentoses
25-51
Fischer proof of structure of glucose
25-52
Fischer started with the aldopentoses
25-53
Experiments on (-) arabinose
Must be an
OH here
25-54
Use KF to get aldohexoses
Fact: Killani Fischer synthesis on (-) arabinose yielded (+) glucose and (+) mannose
CHO
CHO
CHO
HO
OH
HO
K. F.
HO
+
HO
OH
CH2OH
partial
structure of
arabinose
OH
CH2OH
OH
CH2OH
mixture of + glucose and + mannose,
both of unknown structure. Which is
glucose is unknown.
25-55
Aldaric acids from glucose and mannose
Fact: nitric acid oxidation of either glucose or mannose
yields optically active aldaric acids. This locates the OH on
C4 since both aldaric acids have to be active.
C4 OH on right
C4 OH on left
25-56
Which is glucose??
CHO
CHO
HO
OH
HO
+
HO
OH
OH
OH
OH
CH2OH
A
Which one, A or B, is
glucose is determined
by preparing the
aldaric acids
(dicarboxylic acids).
CH2OH
B
25-57
Final piece of data…
Fact: the aldaric acid from (+)glucose is also produced by
nitric acid oxidation of a different aldohexose, (+)gulose.
25-58
Where are we?
 We
have determined the straight chain structure
of (+) glucose. But certain data indicates the
problem is not yet solved.
 Glucose does not give some reactions
characteristic of aldehydes
• A qualitative test, Schiff test, for aldehydes is negative.
• Bisulfite addition products cannot be made
 Mutarotation
changes specific rotation.
 Glucose is converted into two acetals (the methyl
D-glucosides), not hemiacetals, by reaction with
one mole of methanol (acid).
Conclude: glucose is a cyclic hemiacetal.
25-59
Now to determine ring size.
We can methylate the various OH groups,
converting them into OMe. Two kinds of OH
•OH at anomeric carbon
•OH on backbone
One of the backbone OH groups may be
bonded to the anomeric carbon to form a
ring. We seek to detect which one.
First review characteristics of hemiacetals
and acetals.
25-60
Hemiacetals and Acetals, carbonyls and alcohols
Addition
reaction
.
Substitution reaction
(Unstable
in Acid;
Unstable in
base)
(Unstable
in Acid;
Stable in
base)
25-61
Methylation to find ring size.
The observed 4 carbon and
5 carbon dicarboxylic acids
indicate free OH was on C5.
25-62
Conformation of the pyranose ring.
Ring flips can occur. Generally the
conformation with large groups equatorial
dominate.
Generally the CH2OH should be made equatorial
25-63
Extreme case: a-D-Idopyranose
25-64
disaccharides
 Sucrose,
table sugar
 Maltose, from barley
 Lactose, milk sugar
25-65
Sucrose, table sugar
 Table
sugar, obtained from the juice of sugar
cane and sugar beet.
-1, b-2 bond
25-66
Lactose
 The
principle sugar present in milk, 5 – 10%.
25-67
Maltose
 From
malt, the juice of sprouted barley and other
cereal grains.
25-68
Structure Determinatin of (+) Maltose
 Experimental
Facts
C12H22O11
 Positive for Tollens and Fehlings solution,
reducing sugar
 Reacts with phenylhydrazine to yield osazone,
C12H20O9(NNHC6H5)2
 Oxidizes by bromine water to monocaboxylic
acid.
 Exists in two forms which undergo mutarotation.
Consistent with two aldoses linked together with
one hemiacetal group.

25-69
More data…..
 Maltose
undergoes hydrolysis with aq. acid or
maltase to yield two D (+) glucose units. Two
glucose units joined together: glucose – acetal
linkage (glucoside) – glucose – hemiacetal.
 Maltase hydrolysis is characteristic of 
glucosides. Conclude something like
25-70
How to proceed…..
Label the rings and label the free OH groups.
Next
Slide
25-71
Hydrolysis products
Used in
hemiacetal
link.
Not the reducing
aldohexose unit
(not the carboxylic
acid).
Point of
attachment to
the other
glucose unit.
This glucose
derivative was
the “free” CHO
unit, the
Structure on next
reducing
slide.
sugar.
25-72
Maltose
25-73
Starch
 Starch
is used for energy storage in plants
• It can be separated into two fractions; amylose and
amylopectin; each on complete hydrolysis gives only
D-glucose.
• Amylose: A polysaccharide composed of continuous,
unbranched chains of up to 4000 D-glucose units
joined by -1,4-glycosidic bonds.
• Amylopectin: A highly branched polymer of D-glucose;
chains consist of 24-30 units of D-glucose joined by 1,4-glycosidic bonds and branches created by -1,6glycosidic bonds.
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Glycogen
 Glycogen
is the reserve carbohydrate for
animals.
• Like amylopectin, glycogen is a nonlinear polymer of
D-glucose units joined by -1,4- and -1,6-glycosidic
bonds bonds.
• The total amount of glycogen in the body of a wellnourished adult is about 350 g (about 3/4 of a pound)
divided almost equally between liver and muscle.
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Cellulose
 Cellulose:
A linear polymer of D-glucose units
joined by b-1,4-glycosidic bonds.
• It has an average molecular weight of 400,000 g/mol,
corresponding to approximately 2800 D-glucose units
per molecule.
• Both rayon and acetate rayon are made from
chemically modified cellulose.
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Acidic Polysaccharides
 Hyaluronic
acid: An acidic polysaccharide
present in connective tissue, such as synovial
fluid and vitreous humor.
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Acidic Polysaccharides
 Heparin
• Its best understood function is as an anticoagulant.
• Following is a pentasaccharide unit of heparin.
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An example…..
A synthetic polysaccharide is composed of three monosaccharides units
in the following order: (D-glucpyranose) – (L-fructofuranose) – (Daltropyranose).
The linkages between the units and the structures of the individual D units are
given below where the wavy lines are used to avoid specifying configuration.
Add all substituents to the rings and show the linkages between the units.
You must show stereochemistry clearly.
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Solution
Now
L fructose
Now
Now
thethe
 2,6
b ano 25-80
mer
First the D
glucose…
Now the b 1,4
Now
linkD-Altrose