Chapter 25: Carbohydrates

hydrates of carbon: general formula Cn(H2O)n

Plants: photosynthesis h
6 CO2 + 6 H2O C6H12O6 + 6 O2

Polymers: large molecules made up of repeating smaller units

(monomer)

Biopolymers: Monomer units:

carbohydrates (Chapter 25) monosaccharides
peptides and proteins (Chapter 27) amino acids
nucleic acids (Chapter 28) nucleotides

1
1: Classification of Carbohydrates.
Number of carbohydrate units
monosaccharides: one carbohydrate unit
(simple carbohydrates)
disaccharides: two carbohydrate units
(complex carbohydrates)
trisaccharides: three carbohydrate units
polysaccharides: many carbohydrate units
CHO
H OH HO
HO HO
HO H O
HO HO
H OH HO O
HO OH
H OH HO
OH
CH2OH

HO
HO HO O
HO O HO
HO O HO
O HO HO O
HO O HO O
HO O O HO O
HO O HO
HO O
HO HO
HO
OH
O 2
Position of carbonyl group
at C1, carbonyl is an aldehyde: aldose
at any other carbon, carbonyl is a ketone: ketose

Number of carbons
three carbons: triose six carbons: hexose
four carbons: tetrose seven carbons: heptose
five carbons: pentose etc.

Cyclic form (chapter 25.6 and 25.7)

CHO CHO CHO CHO CH2OH

H OH HO H H OH H OH O
CH2OH H OH H OH HO H HO H
CH2OH H OH H OH H OH
CH2OH H OH H OH
CH2OH CH2OH
glyceraldehyde threose ribose glucose fructose
(triose) (tetrose) (pentose) (hexose)
(hexose) 3
(aldohexose) (ketohexose)
25.2: Fischer Projections and the D-L Notation. Representation
of a three-dimensional molecule as a flat structure. Tetrahedral
carbon represented by two crossed lines:
horizontal line is coming vertical line is going back
out of the plane of the behind the plane of the
page (toward you) paper (away from you)
substituent carbon

(R)-(+)-glyceraldehyde
CHO CHO
CHO
H OH H OH
H C
CH2OH CH2OH
HO CH2OH

(S)-(-)-glyceraldehyde
CHO CHO
CHO
HO H HO H
HO C
CH2OH CH2OH CH2OH
H

4
before the R/S convention, stereochemistry was related to (+)-glyceraldehyde
CHO CHO
H OH HO H
CH2OH CH2OH

D-glyceraldehyde L-glyceraldehyde
R-(+)-glyceraldhyde S-(-)-glyceraldhyde
(+)-rotation = dextrorotatory = D (-)-rotation = levorotatory = L

D-carbohydrates have the -OH group of the highest numbered

chiral carbon pointing to the right in the Fisher projection as in
R-(+)-glyceraldhyde

For carbohydrates, the convention is to arrange the Fischer

projection with the carbonyl group at the top for aldoses and
closest to the top for ketoses. The carbons are numbered from
top to bottom.
5
Carbohydrates are designated as D- or L- according to the
stereochemistry of the highest numbered chiral carbon of the
Fischer projection. If the hydroxyl group of the highest numbered
chiral carbon is pointing to the right, the sugar is designated as
D (Dextro: Latin for on the right side). If the hydroxyl group is
pointing to the left, the sugar is designated as L (Levo: Latin for
on the left side). Most naturally occurring carbohydrates are of
the D-configuration.
1 CHO
1 CHO
H 2 OH
3 2
HO H H OH
4 3
H OH HO H
highest numbered 5 4 highest numbered
H OH HO H
"chiral" carbon "chiral" carbon
6 CH2OH 5 CH2OH

D-Glucose L-Arabinose

CHO
HO H CHO

H OH HO H

HO H H OH
highest numbered highest numbered
"chiral" carbon HO H H OH
"chiral" carbon
CH2OH CH2OH
6
L- glucose D-Arabinose
25.3: The Aldotetroses. Glyceraldehyde is the simplest
carbohydrate (C3, aldotriose, 2,3-dihydroxypropanal). The next
carbohydrate are aldotetroses (C4, 2,3,4-trihydroxybutanal).
aldotriose

CHO CHO
H OH HO H
CH2OH CH2OH

D-glyceraldehyde L-glyceraldehyde

aldotetroses
1 CHO 1 CHO
H
2
OH HO 2 H
highest numbered highest numbered
"chiral" carbon H
3
OH HO 3 H "chiral" carbon
4 CH2OH 4 CH2OH

D-erythrose L-erythrose

CHO CHO
HO H H OH
highest numbered highest numbered
H OH HO H
"chiral" carbon "chiral" carbon
CH2OH CH2OH

D-threose L-threose 7
25.4: Aldopentoses and Aldohexoses.
Aldopentoses: C5, three chiral carbons, eight stereoisomers
CHO CHO CHO CHO
H OH HO H H OH HO H
H OH H OH HO H HO H
H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH

D-ribose D-arabinose D-xylose D-lyxose

Aldohexoses: C6, four chiral carbons, sixteen stereoisomers

CHO CHO CHO CHO CHO CHO CHO CHO
H OH HO H H OH HO H H OH HO H H OH HO H
H OH H OH HO H HO H H OH H OH HO H HO H
H OH H OH H OH H OH HO H HO H HO H HO H
H OH H OH H OH H OH H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH

D-allose D-altrose D- glucose D-mannose D-gulose D-idose D-galactose D-talose

8
Manipulation of Fischer Projections
1. Fischer projections can be rotate by 180° (in the plane of the
page) only!
CHO CH2OH CHO CH2OH
180 ° H OH HO H 180 ° HO H H OH
CH2OH CHO CH2OH CHO

(R) (R) (S) (S)

180° 180°

Valid Valid
Fischer Fischer
projection projection

9
a 90° rotation inverts the stereochemistry and is illegal!
90 ° CHO OH
H OH ≠ OHC CH2OH
CH2OH H

(R) (S)
90 °

This is not the correct convention

90° for Fischer projections

Should be projecting toward you

Should be projecting away you

This is the correct convention

for Fischer projections and is
the enantiomer

10
If one group of a Fischer projection is held steady, the other
three groups can be rotated clockwise or counterclockwise.
hold
steady CHO CHO
H OH HO CH2OH
CH2OH H

(R) (R)

CHO H
HO H OHC OH
hold
steady CH2OH CH2OH

(S) (S)

QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
120° QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

120° QuickTime™ and a

TIFF (Uncompressed) decompressor
are needed to see this picture.

hold hold
steady steady hold
steady

QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
120° QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture. 120° QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

hold hold
hold
11
steady steady
steady
ssigning R and S Configuration to Fischer Projections
Assign priorities to the four substitutents according to the
Cahn-Ingold-Prelog rules
Perform the two allowed manipulations of the Fischer projection
to place the lowest priority group at the top or bottom.
If the priority of the other groups 123 is clockwise then
assign the carbon as R, if priority of the other groups 123
is counterclockwise then assign the center as S.
2
place at
CO2H the top 4
H
1 H2N H 4 2 HO2C NH2 1
hold steady CH3
CH3
rotate other 3 3
three groups
counterclockwise
1-2-3 counterclockwise = S
2
4 2
CO2H
H CO2H
4 H 1 2
NH2 1 H 2N
H2N CO2H CH3
CH3 1 3
CH3 H
3 4
3
12
1-2-3 clockwise = R
Fischer projections with more than one chiral center:
1 CHO CHO
2
HO H HO H
3
H OH H OH

4 CH2OH CH2OH
Threose

2
CHO H4
1 2 1
HO
2
H
4
OHC
S 2
OH
3 3
4 H OH 4 H OH 1
Hold Steady 1
3 CH2OH CH2OH
3

(2S, 3R)
H4
H4
Hold Steady 2 1
2
2
1
OHC
2 S OH
OHC OH
3 3
4 H OH 1 1 HO CH2OH
R 3
H
CH2OH
4
3 13
25.5: A Mnemonic for Carbohydrate Configuration.
(please read)

25.6: Cyclic Forms of Carbohydrates: Furanose Forms.

O H+ HO OR2 H+, R2OH R2O OR2
+ R2OH
R1 H R1 H R1 H
(Ch. 17.8)
hemiacetal acetal

O OH OR
H H
H H+, ROH

OH
O Ch. 25.13 O

cyclic hemiacetal mixed acetal (glycoside)

14
In the case of carbohydrates, cyclization to the hemiacetal
creates a new chiral center.
* CHO H OH H H
O O
H OH H H
* + H H *
H OH H H H OH
CH2OH OH OH OH OH

D-erythrose

Converting Fischer Projections to Haworth formulas

15
25.7: Cyclic Forms of Carbohydrates: Pyranose Forms.
H
H
5 OH
H O H
5 O OH
4
H 4
H
1 H H 1 H H 1
CHO HO H
2 3 2 H HO 3
H OH
3 HO OH OH OH
H OH H H H H
4 5 2
1 new chiral
4 3
H OH HO CHO H center
5 H
H H H OH OH OH 5
OH
H H
5 O H
OH H H H
4
H H 1 4
H H 1
D-ribose
HO HO 2 OH
3 2 O 3

HO OH OH OH
ribopyranose

CH2OH 6
6
CH2OH
OH 5
H O H
5 O OH
4
H 4
H
1 OH H 1 OH H 1
CHO HO H
2 2 3 H HO 3
H OH
3
6 H OH H OH
HO H HOH2C H OH H
5 4 3 2
1 new chiral
4
H OH HO CHO 6 CH center
2OH 6
CH2OH
5
HOH2C H H OH H OH 5
OH
6 H H
5 O H
OH H H H
4
OH H 1 4
OH H 1
D-glucose
HO HO 2 OH
3 2 O 3

H OH H OH
glucopyranose 16
25.8: Mutarotation and the Anomeric Effect. The hemiacetal
or hemiketal carbon of the cyclic form of carbohydrates is the
anomeric carbon. Carbohydrate isomers that differ only in the
stereochemistry of the anomeric carbon are called anomers.
Mutarotation: The - and -anomers are in equilibrium, and
interconvert through the open form. The pure anomers can be
isolated by crystallization. When the pure anomers are dissolved
in water they undergo mutarotation, the process by which they
return to an equilibrium mixture of the anomer.
HOH2C Cis
HOH2C
OH -D-Glucopyranose (64%)
HO HO
HO
O
HO
O (-anomer: C1-OH and
CHO
HO HO
OH CH2OH are cis)
H OH H
H
HO H
H OH
HOH2C HOH2C Trans -D-Glucopyranose (36%)
H OH
HO
OH
HO (-anomer: C1-OH and
CH2OH O
HO H HO CH2OH are trans)
D-glucose
H
HO HO
O
OH 17
25.9: Ketoses. Ketoses are less common than aldoses
CH2OH
CH2OH CH2OH CH2OH O
O O O
CH2OH HO H
H OH H OH HO H
O H OH
H OH HO H H OH
CH2OH H OH
CH2OH CH2OH H OH H OH
CH2OH CH2OH
dihydroxyacetone D-ribulose Dxylulose D-fructose D-sedohepuloase

Fructofuranose and Fructopyranose

1
CH2OH 6
6 6
2 CH2OH OH
O HOH2C H OH HOH2C OH O O
1
3 5 4 3 2
H HO 5 H HO 2
HO H HO CH2OH 5
4 3
4 2
CH2OH H CH2OH
H OH H OH H O H 4 3
OH H 1
5 OH H 1
HOH2C H furanose
6
OH

1
CH2OH H 6
H
2 O
6
OH
H H OH H O H 5 O OH
HO 3
H 6
5 4 3 2
1
5
H 4
H
HOH2C CH2OH H HO 2 H HO 2
4
H OH HO CH2OH
5
OH OH H O
3 CH2OH HO 3
H OH 4 1
6 HO H 1 OH H
CH2OH 18
pyranose
25.10: Deoxy Sugars. Carbohydrates that are missing a
hydroxy group.
1 1
CHO CHO
2 2
H OH H H HOH2C OH
HOH2C OH O
3 O 3
H OH H H H OH H H
4 4
H OH H H H OH H H
OH OH 5 CH2OH OH H
5 CH2OH

D-ribose 2-Deoxy-D-ribose

1 1
CHO CHO
6 6
HO
2
H H HO
2
H H
5 O
H
3
OH H
5 O OH H 3
OH H OH
CH2OH CH3
4 4 4
H 4
OH H HO 2 H OH H HO 2

HO 5
H HO H HO 5
H HO H
3 3
6 1 6 1
CH2OH OH H CH3 OH H
L-Galactose 6-Deoxy-L-Galactose
(fucose)

19
25.11: Amino Sugars. Carbohydrates in which a hydroxyl
group is replaced with an -NH2 or -NHAc group

HOH2C HOH2C
HO HO
O O
HO O
OH HO2C OH
HN HN
H CH3
H
O O
N-acetyl-D-glucosamine
N-Acetylmuramic acid
(GlcNAc or NAG)
(MurNAc)

25.12: Branched-Chain Sugars. (Please read)

20
25.13: Glycosides. Acetals and ketals of the cyclic form of
carbohydrates.
O H+ HO OR2 H+, R2OH R2O OR2
+ R2OH
R1 H R1 H R1 H

hemiacetal acetal
CHO
H OH HOH2C HOH2C
HOH2C
HO H HO ROH HO
O O HO
H OH HO HO + O
OH H+ OR HO
H OH HO HO H
HO
CH2OH H H
pyranose Glycoside OR
D-glucose (hemiacetal) (acetals)

Note that only the anomeric hydroxyl group is replaced by ROH

21
25.14: Disaccharides. A glycoside in which ROH is another
carbohydrate unit (complex carbohydrate).
OH HO
OH
HO OH
HO O
HO HO OH HO
HO O O OH HO
H OH HO O HO
O HO
HO HO O O
HO HO O O
O H HO
O HO H O
HO OH HO OH
OH
HO OH HO

ce llobiose Lactose sucrose

m altose (1,2'-g lycoside ) OH
(1,4'-α-g lycoside ) (1,4'-β-g lycoside ) (1,4'-β-g lycoside )

25.15: Polysaccharides. Cellulose: glucose polymer made up

of 1,4’--glycoside linkages
HO HO HO HO HO HO
O O O O O O
O O O O O O O
HO HO HO HO HO HO HO
HO HO HO HO HO
H H H H H H

Amylose: glucose polymer made up of 1,4’--glycoside linkages

HO HO HO HO
O H O H H H
HO HO
O O H H
O O
O O
HO HO O O 22
HO HO HO HO O O
HO HO HO HO O
HO HO
Amylopectin:
OH
O
HO O
H OH
HO
O O
HO
HO
HO HO HO O
O H O H H H
HO HO
O O H H
O O
O O
HO HO O O
HO HO HO HO HO HO
O O
HO HO HO HO
O

25.16: Reactions of Carbohydrates. Glycoside formation is

related to acetal formation.
25.17: Reduction of Monosaccharides. C1 of aldoses are
reduced with sodium borohydride to the 1° alcohol (alditols)
Reacts like
A carbonyl CHO CH2OH
HOH2C H OH H OH
HO HO H NaBH4 HO H
O
HO H OH H OH
HO H OH H OH
OH
CH2OH CH2OH

D-glucose D-glucitol

23
Reduction of ketoses CH2OH CH2OH CH2OH
O H OH HO H
HO H NaBH4 HO H HO H
+
H OH H OH H OH
H OH H OH H OH
CH2OH CH2OH CH2OH

D-fructose D-glucitol D-mannitol

25.17: Oxidation of Monosaccharides. C1 of aldoses can be

selectively oxidized to the carboxylic acid (aldonic acids) with
Br2 or Ag(I) (Tollen’s test).
CHO CO2H
H OH Ag(I) Ag(0) H OH
HO H HO H
H OH H OH
NH3,
H OH H OH
H2O
CH2OH CH2OH
aldonic acid
CO2H
HOH2C HOH2C H OH
HO Br2 HO H2O
O O HO H
HO HO
H OH
HO HO
OH H OH
O
CH2OH

Reducing sugars: carbohydrates that can be oxidized to aldonic

acids. 24
Oxidation of aldoses to aldaric acids with HNO3.
CHO CO2H
H OH H OH
HNO3 HO H
HO H
H OH H OH
H OH H OH
CH2OH CO2H
Glucaric acid

Uronic Acid: Carbohydrate in which only the terminal -CH2OH is

oxidized to a carboxylic acid.
CHO CHO
H OH H OH HO2C
[O] HO H HO
HO H O
H OH H OH
HO
H OH H OH HO
OH
CH2OH CO2H
Gluronic acid

25
Reducing sugars: carbohydrates that can be oxidized to aldonic
acids.
HO HO HO
HO HO HO
HO HO HO O
O HO O Ag(I) HO
HO O O O + Ag(0)
O OH OH
HO HO HO HO HO HO
H [O] OH
HO HO HO
OH
O O
reducing
end
cellobiose and maltose
are reducing sugar
HO HO HO HO Ag(I) HO HO
HO HO HO + Ag(0)
O 4' O [O] O
HO O HO HO
O O OH O OH
HO HO HO HO HO
1 H HO OH
HO HO HO
OH O O
lactose
reducing
(1,4'-β-g lycoside ) end
lactose is a
reducing sugar
HO
HO O Ag (I)
HO HO No re action
HO 1 α [O]
g lucose O
OH
O fructose sucrose is not
sucrose HO a reducing sugar
(1,2'-g lycoside ) No re d ucing e nd
OH
26
25.19: Cyanohydrin Formation and Chain Extension.
Kiliani-Fischer Synthesis- chain lengthening of monosaccharides

27
 Determination of carbohydrate stereochemistry

1) HCN CHO CO2H

2) H2, Pd/BaSO4 HNO3,
H OH H OH
3) H2O heat
H OH H OH
CH2OH CO2H
D-(-)-erythrose
tartaric acid
CHO
H OH Killiani-Fischer
CH2OH synthesis

D-(+)-glyceraldehyde

CHO
HNO3, CO2H
HO H heat HO H
H OH
H OH
1) HCN
CH2OH
2) H2, Pd/BaSO4 CO2H
3) H2O
D-(-)-threose
D-(-)-tartaric acid

28
 1) HCN CHO CO2H
2) H2, Pd/BaSO4
3) H2O H OH HNO3, H OH
H OH heat
H OH
H OH H OH
CH2OH CO2H
D-(-)-ribose
ribonic acid
CHO
H OH Killiani-Fischer
H OH synthesis
CH2OH

D-(-)-erythrose
CHO CO2H
HO H HNO3, HO H
heat
H OH H OH
1) HCN
H OH H OH
2) H2, Pd/BaSO4
3) H2O CH2OH CO2H
D-(-)-arabinose arabonic acid

29
 1) HCN CHO CO2H
2) H2, Pd/BaSO4 HNO3,
H OH H OH
3) H2O heat
HO H HO H
H OH H OH
CH2OH CO2H
D-(+)-xylose xylonic acid
CHO
HO H Killiani-Fischer
H OH synthesis
CH2OH

D-(-)-threose
CHO CO2H
HO H HNO3, HO H
heat
HO H HO H
1) HCN
H OH H OH
2) H2, Pd/BaSO4
3) H2O CH2OH CO2H

D-(-)-lyxose lyxonic acid

30
 CHO CHO CHO CHO
H OH HO H H OH HO H
H OH H OH HO H HO H
H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH

D-ribose D-arabinose D-xylose D-lyxose

CHO CHO CHO CHO CHO CHO CHO CHO

H OH HO H H OH HO H H OH HO H H OH HO H
H OH H OH HO H HO H H OH H OH HO H HO H
H OH H OH H OH H OH HO H HO H HO H HO H
H OH H OH H OH H OH H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH

D-allose D-altrose D- glucose D-mannose D-gulose D-idose D-galactose D-talose

CO2H CO2H CO2H CO2H CO2H CO2H CO2H CO2H

H OH HO H H OH HO H H OH HO H H OH HO H
H OH H OH HO H HO H H OH H OH HO H HO H
H OH H OH H OH H OH HO H HO H HO H HO H
H OH H OH H OH H OH H OH H OH H OH H OH
CO2H CO2H CO2H CO2H CO2H CO2H CO2H CO2H

optically optically optically optically optically optically optically optically

inactive active active active active active inactive active

enantiomers
31
25.20: Epimerization, Isomerization and Retro-Aldol Cleavage.
O HO , OH HO , O
H2O H2O From
CH2CH3 CH2CH3 CH2CH3
C6H5 C6H5 C6H5 Ch 18.10
H CH3 CH3 H3C H

O OH O
H H H
C C C
(R) (S)
H OH OH HO , HO H
HO ,
HO H HO H H2O HO H
H2O
H OH H OH H OH
H OH H OH H OH
CH2OH CH2OH CH2OH
D-glucose D-mannose

HO ,
H2O

CH2OH
O
HO H Fructose is a reducing sugar
H OH (gives a positive Tollen’s test)
H OH
CH2OH
D-fructose

32
Retro-aldol reaction of carbohydrates
CH2OH
CH2OH
O H O
O CH2OH H-B CH2OH
HO H
HO H H OH + O O
H O H
:B H O CH2OH HO H CH2OH
H OH
H OH
CH2OH
CH2OH D-Glyceraldehyde Dihydroxyacetone
D-fructose

Glycolysis
O
H CH2OH
C
phosphoglucose phosphofructo-
phosphoglucose O isomerase
H OH kinase
isomerase 2-O POH C
O CH2OH
HO H HO H 3 2

H OH HO
H OH
OH
H OH H OH
CH2OPO32- OH
CH2OPO32-
α-D -fructofuranose -
D-glucose-6-phosphate D-fructose-6-phosphate 6-phosphate

CH2 OPO 3 2-
2-O POH C
3 2 O CH2OPO32-
aldolase O aldolase CH2 OPO 3 2- CHO
HO HO H O + H OH
OH
H OH CH2 OH CH2 OPO 3 2-
OH H OH
D ihydroxyace tone D -g lyce ralde hyde -
D -fructose - CH2 OPO 3 2- phosphate 3-phosphate
1,6-bisphosphate
D -fructose -
1,6-bisphosphate
33
triose phosphate
isom e rase
25.21: Acylation and Alkylation of Hydroxyl Groups
Acylation (ester formation): O
H3 C
O O O
HO O
H3 C O CH3 H3 C
HO O
HO O O
OH O CH3
HO O
pyridine H3 C O
O O
β-D -g lucopyranose O CH3

Alkylation (ether formation):

O
H
C
HO H3 CO
Ag 2 O, CH3 I H3 CO H3 O + H OCH3
HO H3 CO O
HO O H3 CO O H3 CO
OH H3 CO H3 CO H
HO OCH3 H3 CO
H3 CO OH H OCH3

β-D -g lucopyranose H OCH3

CH2 OCH3

25.22: Periodic Acid Oxidation. The vicinal diols of

carbohydrate can be oxidative cleaved with HIO4.
34