Carbohydrates
Part (I)
1. Source and application of carbohydrates
2. Classification of carbohydrates
3. Carbohydrate stereochemistry
4. Cyclic Structures of Monosaccharides
5. Reactions of monosaccharide
6. Chain lengthening: The Kiliani–Fischer Synthesis
7. Chain shortening: The Wohl Degradation
1. Source and application of carbohydrates:
carbon hydrates, Cn(H2O)n
the empirical formulas, (C(H2O))n
2. Classification of Carbohydrates
—— based on hydrolysis
• Simple sugars (monosaccharides) can't be converted into
smaller sugars by hydrolysis.
• Carbohydrates are made of two or more simple sugars
connected as acetals (aldehyde and alcohol), oligosaccharides
and polysaccharides
• Sucrose (table sugar): disaccharide from two monosaccharides
(glucose linked to fructose)
• Cellulose is a polysaccharide of several thousand glucose units
connected by acetal linkages (aldehyde and alcohol)
A disaccharide
derived from
cellulose
Classification of Carbohydrates
—— based on fuctional groups, Aldoses and Ketoses
• aldo- and keto- prefixes identify the nature of the carbonyl
group
• -ose suffix designates a carbohydrate
• Number of C’s in the monosaccharide indicated by root (-tri-,
tetr-, pent-, hex-)
Summary of Classifications:
Complexity
Simple Carbohydrates
monosaccharides
Size
Tetrose
C4 sugars
C=O
Function
Reactivity
Pentose
C5 sugars
Complex Carbohydrates
disaccharides, oligosaccharides
& polysaccharides
Hexose
C6 sugars
Heptose
C7 sugars
etc.
Aldose
sugars having an aldehyde function or an acetal equivalent.
Ketose
sugars having a ketone function or a ketal equivalent.
Reducing
sugars oxidized by Tollens' reagent (or Benedict's or Fehling's reagents).
Non-reducing
sugars not oxidized by Tollens' or other reagents.
3. Carbohydrate Stereochemistry: Fischer Projections
• Carbohydrates have multiple chirality centers
• A chirality center C is projected into the plane of the paper and
other groups are horizontal or vertical lines
• Groups forward from paper are always in horizontal line.
• The oxidized end of the molecule is always higher on the page
(―up‖)
Fischer Projections
Chair Form
To an aldohexose:
2n stereoisomers: 16
absolute configurations (R, S)
relative configurations (D, L)
8 D-forms and 8 L-forms
The sign of a compound's specific rotation (an experimental
number) does not correlate with its configuration (D or L).
Relative configurations (D, L)
—Stereochemical Reference
• The reference compounds are the two enantiomers of
glyceraldehyde, C3H6O3
• D-glyceraldehyde is (R)-2,3-dihydroxypropanal
• L-glyceraldehyde is (S)-2,3-dihydroxypropanal
Four Carbon Aldoses
• Aldotetroses have two chirality centers
• There are 4 stereoisomeric aldotetroses, two pairs of
enantiomers: erythrose and threose
• D-erythrose is a a diastereomer of D-threose and L-threose
Minimal Fischer Projections
• In order to work with structures of aldoses more easily, only
essential elements are shown
• OH at a chirality center is ―‖ and the carbonyl is an arrow 
• The terminal OH in the CH2OH group is not shown
Aldopentoses
• Three chirality centers and 23 = 8 stereoisomers, four pairs of
enantiomers: ribose, arabinose, xylose, and lyxose
• Only D enantiomers are shown
 All altruists gladly make gum in gallon tanks
D-family of aldohexose:
4. Cyclic Structures of Monosaccharides
—— Hemiacetal Formation
• Alcohols add reversibly to aldehydes and ketones, forming
hemiacetals and hemiketals
Internal Hemiacetals of Sugars
•
•
•
•
Intramolecular nucleophilic addition creates cyclic hemiacetals in sugars
Five- and six-membered cyclic hemiacetals are particularly stable
Five-membered rings are furanoses. Six-membered are pyanoses
Formation of the the cyclic hemiacetal creates an additional chirality
center giving two diasteromeric forms, designated  and b
• These diastereomers are called anomers
• The designation  indicates that the OH at the anomeric center is on the
same side of the Fischer projection structure as hydroxyl that designates
whether the structure is D or L
Fischer Projection Structures of Anomers: Allopyranose from
Allose
Converting to Proper Structures — Haworth formula
 Note that all bonds on the same side of the Fischer projection will be cis in
the actual ring structure
Representative chair conformer of pyranoses
• Pyranose rings have a chair-like geometry with axial and
equatorial substituents
• Rings are usually drawn placing the hemiacetal oxygen atom
at the right rear
representative chair conformer
Mutarotation
• The two anomers of D-glucopyranose can be crystallized and
purified
– -D-glucopyranose melts at 146oC and its specific
rotation []D = 112.2°;
– b-D-glucopyranose melts at 148–155oC and specific
rotation []D = 18.7°
• Rotation of solutions of either pure anomer slowly change
due to slow conversion of the pure anomers into a 37:63
equilibrium mixture ot :b called mutarotation
Mechanism of Mutarotation Glucose
• Occurs by reversible ring-opening of each anomer to the
open-chain aldehyde, followed by reclosure
• Catalyzed by both acid and base
5. Reactions of Monosaccharides
• OH groups can be converted into esters and ethers,
– Esterification by treating with an acid chloride or acid
anhydride in the presence of a base
– All -OH groups react
Ether Formation
• Treatment with an alkyl halide in the presence of base—the
Williamson ether synthesis
• Use silver oxide as a catalyst with base-sensitive compounds
Glycoside Formation
• Treatment of a monosaccharide hemiacetal with an alcohol and an acid
catalyst yields an acetal in which the anomeric -OH has been replaced by
an -OR group
– b-D-glucopyranose with methanol and acid gives a mixture of  and b
methyl D-glucopyranosides
 Carbohydrate acetals are named by first citing the alkyl group and
then replacing the -ose ending of the sugar with –oside
Selective Formation of C1-Acetal
• Synthesis requires distinguishing the numerous OH groups
• Treatment of glucose pentaacetate with HBr converts anomeric OH to Br
• Addition of alcohol (with Ag2O) gives a b glycoside (Koenigs–Knorr
reaction)
Koenigs-Knorr Reaction Mechanism
•  and b anomers of tetraacetyl-D-glucopyranosyl bromide give b glycoside
• Suggests either bromide leaves and cation is stabilized by neighboring
acetyl nucleophile from  side
• Incoming alcohol displaces acetyl oxygen to give b glycoside
Reduction of Monosaccharides
• Treatment of an aldose or ketose with NaBH4 reduces it to a polyalcohol
(alditol)
• Reaction via the open-chain form in the aldehyde/ketone hemiacetal
equilibrium
Oxidation of Monosaccharides
• Aldoses are easily oxidized to carboxylic acids by:
Tollens' reagent (Ag+, NH3),
Fehling's reagent (Cu2+, sodium tartarate),
Benedict`s reagent (Cu2+ sodium citrate)
• Oxidations generate metal mirrors; serve as tests for “reducing” sugars
(produce metallic mirrors)
• Ketoses are reducing sugars if they can isomerize to aldoses
Oxidation of Monosaccharides with Bromine
• Br2 in water is an effective oxidizing reagent for converting aldoses to
carboxylic acid, called aldonic acids (the metal reagents are for analysis
only)
Formation of Dicarboxylic Acids
• Warm dilute HNO3 oxidizes aldoses to dicarboxylic acids, called aldaric
acids
• The -CHO group and the terminal -CH2OH group are oxidized to COOH
1.
2.
3.
Osazone Formation
1.
2.
Epimerization and isomerization —— base catalyzed:
H
base:
H
O
O
H+
OH
HO
H
H
OH
H
OH
CH2OH
H
HO
OH
H
H
OH
H
OH
CH2OH
H
O
H
OH
HO
H
H
OH
H
OH
CH2OH
O
HO
HO
H
H
H
OH
H
OH
CH2OH
epimer
D-mannose
HOH
H
O
OH
HO
H
H
OH
H
OH
CH2OH
D-glucose enolate
H
OH
OH
HO
H
H
OH
H
OH
CH2OH
OH
H
OH
O
HO
H
H
OH
H
OH
CH2OH
H
OH
HOH
O
HO
H
H
OH
H
OH
CH2OH
H
OH
O
HO
H
H
OH
H
OH
CH2OH
D-fructose
Fischer Phenylhydrazone and Osazone Reaction
—why 3 PhNHNH2
Malaprade reaction —— oxidative cleavage of vicinal diol
HOCH2(CHOH)4CHO + 5 HIO4
Glycol Cleavage:
H2C=O + 5 HCO2H + 5 HIO3
6. Chain Lengthening: The Kiliani–Fischer Synthesis
• Lengthening aldose chain by one CH(OH), an aldopentose is converted into
an aldohexose
Kiliani-Fischer Synthesis Method
• Aldoses form cyanohydrins with HCN
– Follow by hydrolysis, ester formation, reduction
• Modern improvement: reduce nitrile over a palladium
catalyst, yielding an imine intermediate that is hydrolyzed to
an aldehyde
Stereoisomers from Kiliani-Fischer Synthesis
• Cyanohydrin is formed as a mixture of stereoisomers at the
new chirality center, resulting in two aldoses
7. Chain Shortening: The Wohl Degradation
• Shortens aldose chain by one CH2OH
Chain Shortening: The Ruff Degradation
Using these reactions we can now follow Fischer's train of logic in
assigning the configuration of D-glucose.
1. Ribose and arabinose (two well known pentoses) both gave erythrose on
Ruff degradation.
As expected, Kiliani-Fischer synthesis applied to erythrose gave a mixture
of ribose and arabinose.
2. Oxidation of erythrose gave an achiral (optically inactive) aldaric acid. This
defines the configuration of erythrose.
3. Oxidation of ribose gave an achiral (optically inactive) aldaric acid. This
defines the configuration of both ribose and arabinose.
4. Ruff shortening of glucose gave arabinose, and Kiliani-Fischer synthesis
applied to arabinose gave a mixture of glucose and mannose.
5. Glucose and mannose are therefore epimers at C-2, a fact confirmed by
the common product from their osazone reactions.
6. A pair of structures for these epimers can be written, but which is glucose
and which is mannose?
1. Source and application of carbohydrates
2. Classification of carbohydrates
3. Carbohydrate stereochemistry
4. Cyclic Structures of Monosaccharides
5. Reactions of monosaccharide
6. Chain lengthening: The Kiliani–Fischer Synthesis
7. Chain shortening: The Wohl Degradation