Chemistry

Dr. Kamala Das Dey

HOD
Dept. of Microbiology
Bankura Sammilani College
 carbohydrates
Historical MYTH

“hydrates of carbon”
Molecular formula:
According
to Cn(H2O)n, where n is 3 or more
MODERN SCIENCE

Structural studies revealed that these compounds were not hydrates because they
did not contain intact water molecules, but the term “carbohydrate” persists
because the most of the carbon atoms formally have a molecule of water attached
in the form of a H and an OH.

More precisely CARBOHYDRATES are designated as polyhydroxy aldehyde

or polyhydroxy ketone.
The chemical structures of carbohydrates arecommonly represented by wedge-and-dash
structures or by Fischer projections.

“sweet sand”
terms “carbohydrate,” “saccharide,” and “sugar” are often used
interchangeably.“Saccharide” means „sugar‟ comes from the word in several
early languages (sarkarainSanskrit, sakcharonin Greek, and saccharumin
Latin). Sugar is a combination of the Sanskritwords su (sweet) and gar (sand).
 CARBOHYDRATES

SUGARS POLYSACCHARIDES

MONOSACCHARIDES OLIGOSACCHARIDES
SUGAR: Simples carbohydrates are known as sugars and the ending of
the names of sugar is –ose. Most of the cases they are crystalline,
soluble in water and are sweet substance.

Monosaccharides:
These are sugars which cannot be hydrolysed into smaller carbohydrates.
The most common monosaccharides have three to eight carbon atoms. The
suffix-ose indicates that a molecule is a simple carbohydrate, and the
prefixes tri-, tetr-,pent-, and so on indicate the number of carbon atoms in
the chain. Monosaccharides containing an aldehyde group are classified as
aldoses(ald- is for aldehyde and -oseis the for a sugar ) those containing a
ketone group are classified as ketoses. A ketose can also be indicated with
the suffix ulose; thus, a five- carbon ketose is also termed a Pentulose.
e.g., Glucose, Fructose etc..
Oligosaccharides:
(‘Oligo’ is a Greek word means ‘few’). Carbohydrates that hydrolyse to yield 2-10
molecules of monosaccharides.
e.g., Sucrose, maltose- disaccharide

1 mole of raffinose 1 mole galactose + 1 mole glucose + 1 mole fructose

A trisaccharides
The Cyclic Structure of Monosaccharides
We know that aldehydes and ketones react with alcohols to for mhemiacetals.
when hydroxyl and carbonyl groups are part of the same molecule, the cyclic
hemiacetals form very readily and their interaction can form a five or six-membered ring.
For example, 4-hydroxypentanal forms a five-membered cyclic hemiacetal.

Note that 4-hydroxypentanal contains one chiral center and that a second chiral
centeris generated at carbon 1 as a result of hemiacetal formation. Monosaccharides
have hydroxyl and carbonyl groups in the same molecule. As a result, they too exist
almost exclusively as five- and six-membered cyclic hemiacetals.
 Examples of cyclic structure of D Glucose

The cyclic hemiacetal that has a five-membered ring is called a furanose. This name is
derived from that of the five-membered, oxygen-containing heterocyclic compound furan.
The hemiacetal with a six-membered ring is known as a pyranose after the heterocycle
pyran.
As we know six-membered rings are generally more stable than fivemembered rings,
primarily because of increased torsional strain in the latter. Therefore, it is not surprising
that the pyranose form of a monosaccharide is usually more stable than the furanose
form. At equilibrium, glucose exists primarily as the pyranose (>99.8%), with little, if any,
furanose (<0.2%) present. There is also a trace amount (0.02%) of the uncyclized aldehyde
present. Of course, this equilibrium depends on the structure of the monosaccharide, and
some other sugars have larger amounts of the furanose form.

Haworth Projecions
Tollens (1883) suggested an oxide ring structure of glucose. Letter Howarth, Hist
and their co-workers (1926 onwards) established that carbohydrates exist as cyclic
hemiacetal rather than open-chain forms and cyclic representation of carbohydrates are
called Howarth formulas according to the name of English chemist Sir Walter N. Haworth
(1937Nobel Prize in Chemistry). It is a very common way of representing the cyclic
structure of monosaccharides. In a Haworth projection, a five- or six-member
cyclichemiacetal is represented as a planar pentagon or hexagon, as the case may be,
lyingperpendicular to the plane of the paper.Groups bonded to the carbons of the
ringthen placed either above or below the plane of the ring.
Conversion of an Aldohexose (D-Glucose) to Howarth Pyranose form..

1. Mentally lay down the Fischer projection on its right side. The groups that wereon the
right in the Fischer projection are now ‘down’ and the groups that were on the left are
‘up’.
2. C5 and C6 curls back away from you. The C4-C5 bond must be rotated so that the C5
hydroxyl group can form a part of the ring (i.e., for the formation of a planar ring). For a
sugar of the D series, this rotation puts the terminal –CH2OH (C6 in glucose) upward.
3. Close the ring, and draw the result. When drawing Howarth projection of a pyranose
ring, the convention is to place the oxygen atom in the upper, rear-right corner, of the
six membered ring, with C1 at the far right.C1 is easily identified because it is the
hemiacetal carbon.
When a pyranose or furanose ring closes, the flat carbonyl group is converted to an
asymmetric carbon in the hemiacetal. Depending on which face of the carbonyl
group is attacked, the hemiacetal–OH group can be directed either up or down.
The new chiral center created informing the cyclic structure is called an anomeric carbon.
Stereoisomers that differ in configuration only at the anomeric carbon are called
anomers.‘Ano’ is Greek for ‘Upper’, thus anomers differ in configuration at the upper-most
asymmetric carbon(the hemiacetal or acetal carbon) of the cyclic form of carbohydrate. The
anomeric carbonof an aldose is carbon 1; that of D-fructose, the most common ketose, is
carbon 2.

The hemiacetal carbon atom is called the anomeric carbon and its -OH group is called the
anomeric hydroxyl group.For D-series of sugars the structure with the anomeric -OH group
‘down’ to the plane of ring is called the (alpha) anomer, and the one with the anomeric
group ‘up’ to the plane of ring is called the β (beta) anomer.

Another way to remember the anomers, that the designation β- means the –OH on the
anomeric carbon of the cyclic hemiacetal is on the same side of the ring asthe terminal -
CH2OH. Conversely, the designation α- means that the –OH on the anomeric carbon of the
cyclic hemiacetal is on the side of the ring opposite the terminal -CH2OH.
Cyclic Structure for L-Sugars
L- sugars are the COMPLETE enantiomers [mirror images] of the corresponding
D- sugar of the same name. Therefore for L-serise of sugar, designation of α- or
β-isomer →take the mirror image of the D-isomer (α or β) of that sugar.
Three-Dimensional Representations of Pyranose Rings
We have seen that Haworth projections are often used for drawing the cyclic
forms of D-glucose. While Haworth projections are extremely useful for showing
configurations, they are not effective for communicating the conformation of a compound.
X-ray crystallographic studies shows that the six-membered pyranose ring of D-glucose
adopts a chair conformation.
Drawing the chair conformation of a pyranosering:
When drawing either a Haworth projection or a chair conformation, the convention is to
place the oxygen atom in the upper, rear-right position,

Step 1 The first step is to draw

the Haworth projection of the
compound
Step 2 Draw the skeleton of a chair conformation with an oxygen atom in the upper,
rear-right position.
Step 3 Draw each substituent as UP or DOWN on the chair

Like cyclohexane, the 6–membered ring of monosaccharides also exists in two isomeric
chairconformations, which are specified as 1C4 and 4C1, respectively, where the letter C
stands for 'chair' and the numbers indicate the carbon atoms located above or below the
reference plane of the chair, made up by C–2, C–3, C–5 and the ring oxygen.

The conformational shape of a pyranose is mainly governed by the relative stability of the
two possible chair conformations which are both free of torsional strain, but one of which,
in most cases, is clearly energetically unfavored because of van der Waals interactions of the
ring substituents.
Thus, the 1C4 conformation of β–D–glucopyranose is clearlyunfavored compared to its 4C1
conformation because the van der Waals repulsion of the 1,3–diaxially positioned ring
substituent’s.
Problem: Draw the most stable conformations of α-D-Glucose and β-D-mannose in polar
solvent
Draw β-L-glucopyranose in its more stable chair conformation.
It’s probably easiest to begin by drawing the chair conformation of β-D-glucopyranose.
Then draw its mirror-image L enantiomer by changing the stereochemistry at every position
on the ring, and carry out a ring-flip to give the more stable chairconformation. Note that
the -CH2OH group is on the bottom face of the ring in the L enantiomer as is the anomeric -
OH.
Chair conformation of Ketohexose (D-Fructose)
D-Fructose,exists in water solution as70% β-pyranose, 2% α-pyranose, 0.7% open-chain,
23% β-furanose, and 5%α-furanose. The pyranose form results from addition of the -OH at
C6 to thecarbonyl group, while the furanose form results from addition of the -OH atC5 to
the carbonyl group
MUTAROTATION: (from ‘mutation’ meaning change)

The change in specific rotation that occurs when an α or βhemiacetal form of a freshly
prepared carbohydrate in aqueous solution is converted to an equilibrium mixture of the
two forms.
When crystals of pure α-D-glucose are dissolved in water, the specific rotation
gradually changes from +112.20to +52.70 and remains constant at this value. Similarly when
crystals of pure β-D-glucose are dissolved in water, the specific rotation gradually changes
from +18.70 to +52.70.
This change in rotation occurs because, in water (behave as amphiprotic solvent),
the hemiacetal opens to form the aldehyde and, when the aldehyde recyclizes, both α-D-
glucose and β-D-glucose can be formed. Eventually, the three forms (open-chain, α-, and β-
) of glucose reach equilibrium concentrations. The specific rotation of the equilibrium
mixture is +52.70.The equilibrium mixture consists of 64% β-D-glucopyranose and 36% α-D-
glucopyranose. It contains only traces (0.003%) of the open-chain form. Mutarotation is
common to all carbohydrates that exist in hemiacetal forms.
Anomeric Effect
The equatorially positioned substituents of a carbohydrate ring are, for steric
reasons,
the most energetically favored, compared to their axial counterparts, as is the case in every
molecule with a chair conformation. However, the anomerically bound groups in
carbohydrates do not follow this rule completely: For D–pyranoses, D–pyranosides and
especially carbohydrate derivatives with electronegative groups at the anomeric center the
anomeric α–configured derivatives with the anomeric group located in an axial position are
often more stable than would be predicted from the steric interactions they have with
adjacent substituents. An aqueous solution of D–glucose, for example, contains the α– and
theβ–form in a ratio of 35:64, and the effect is even pronounced for D–mannose, where the
α:β–ratio is 69:30.
It is not possible to tell by inspection which pyranose form (α or β) of a particular
carbohydrate predominates at equilibrium. In addition to the usual factors that govern the
equatorial vs axial orientation of the substituents on a six membered ring two others factors
are important
(i) An equatorial –OH is less crowded and better solvated by polar solvent(e.g.,
water) than axial one.
(ii) Anomeric effect: When the anomeric carbon bearing an electronegative
substituent, the unusual preference of the substituent to the sterically unfavored axial
position over the equatorial position at the anomeric center has been termed the
‘anomeric effect’ by R. Lemieux.
The anomeric effect was discovered in the case of carbohydrates but has been found tobe
of general importance for molecules, where two heteroatoms are bound to a tetrahedral
center. Thus, the essential group for the appearance of an anomeric effect is:

The anomeric effect can be explained in several ways. It partly involves a dipole-dipole
effect based on intramolecular electrostatic interactions of two dipoles. One of the two
dipoles arises from the two lone electron pairs of the endocyclic carbohydrate ring oxygen.
The other dipole points along the polarized bond between the anomeric carbon atom and
its bound atom X. Anomeric configurations, where the two dipoles partially neutralize each
other are favored over the diastereomers where the anomeric configuration leads to partial
intramolecular addition of the two dipoles.
The anomeric effect is different for every specific case. It is also strongly influencedby
the substituent at C–2. When this is equatorial, as in glucose and galactose, the
anomeric effect is weakened, and is enhanced in the case of an axial C–2–substituent
as inmannose. Moreover, the nature of the anomeric group is of crucial influence for
the anomeric effect, as it is proportional to the electronegativity of the anomerically
bound atom. Solvents also influence the anomeric effect, such that increased polarity
of the solvent used decreases the influence of the anomeric effect on the
equilibration of the two alternative conformers in solution
 TABLE : α- and β-Pyranose and Furanose Forms of the Aldohexoses at 25 °C in Water

Reactions of Monosaccharides
Because monosaccharides exist in solution in an equilibrium between acyclic and cyclic
forms, they undergo three types of reactions:

(1) Reaction of the anomeric hydroxyl groups

(2) Reaction of the hydroxyl groups
(3) Reaction of the carbonyl group

Note, that monosaccharides have two different types of OH groups. Most are “regular”
alcohols, and as such, undergo reactions characteristic of alcohols. On the other hand, the
anomeric OH group, is part of a hemiacetal, giving it added reactivity
Glycoside (Acetal) Formation
Glycosides are acetals with an alkoxy group (OR) bonded to the anomeric carbon.
Note: “glycoside is the functional group name for any sugar whereas a glucoside is formed
specifically from glucose”
Treatment of a monosaccharide with an alcohol and HCl converts the hemiacetal into an
acetal called a glycoside.
The mechanism explains why only the hemiacetal OH group reacts. Protonation of the
hemiacetal OH, followed by loss of H2O, forms a resonance-stabilized carbocation in
Step [2]. A resonance-stabilized carbocation is not formed by loss of H2O from any other
OH group.
Glycoside Hydrolysis
Glycosides are stable in basic solutions because they are acetals. In acidic solutions,
however, glycosides undergo hydrolysis to produce a sugar and an alcohol (again, because
they are acetals). The alcohol obtained by hydrolysis of a glycoside is known as an
aglycone:

Mechanism
Steps [1]–[2] Protonation and loss of the leaving group
Steps: [3]–[4] Nucleophilic attack and deprotonation

Nucleophilic attack of H2O on the planar carbocation occurs from both sides to yield α
and β anomers after loss of a proton.
Reactions of Monosaccharides at the OH Groups
Because monosaccharides contain OH groups, they undergo reactions typical of alcohols—
that is, they are converted to ethers and esters.

Formation of Ether
When dealing with monosaccharides, a strong base cannot be used and instead, a mild
base such as silver oxide is used. Under these conditions, all five hydroxyl groups of
β-D-glucopyranose are converted into ether groups.
e.g., α-D-glucose reacts with silver(I) oxide (Ag2O, a base) and excess CH3I to form a
pentamethyl ether.

Ag2O removes a proton from each alcohol, which then reacts with CH3I in an SN2 reaction.
Because no C – O bonds are broken, the configuration of all substituents in the starting
material is retained, forming a single product.
HYDROLYSIS
The four ether bonds that are not part of the acetal do not react with any reagents except
strong acids like HBr and HI. The acetal ether, on the other hand, is hydrolyzed with
aqueous acid. Aqueous hydrolysis of a single glycoside (like the pentamethylether of α-D-
glucose) yields both anomers of the product monosaccharide.

One of the most important aspects of sugar chemistry is the inability to use basic
reagents because they cause unwanted side reactions. Two common base-catalyzed
side reactions are epimerization and enediol rearrangement.
EPIMERIZATION
Epimers: Any pair of diastereomers that differ in configuration at only a single tetrahedral
chirality center are called epimers.

Under basic conditions, the proton alpha to the aldehyde (or ketone) carbonyl group is
reversibly removed In the resulting enolate ion, C2 is no longer asymmetric, and its
stereochemistry is lost. Re-protonation can occur on either face of the enolate, giving
either configuration. The result is an equilibrium mixture of the original sugar (D-
Glucose) and its C-2 epimer (D-Mannose). Because a mixture of epimer results, this
stereochemical change is called epimerisation.
Another base-catalyzed side reaction is the enediol rearrangement

Anomers are special cases of epimers that differ in configuration only at the anomeric
carbon. Both cyclic forms of glucose, α-glucopyranose and β-glucopyranose are also a type
of Epimers which are differ from each other at anomeric carbon atom and also known
as anomers of each other.
Reactions at the Carbonyl Group
Reactions of Monosaccharides with Phenylhydrazine: Osazones

Oxidation Reactions of Monosaccharides: Reducing Sugars

 Examples of reducing and non-reducing sugars

Bromine Water oxidation: The Synthesis of Aldonic Acids

Bromine water is a mild acidic reagent that selectively oxidizes the -CHO group to a -
CO2H group, thus converting an aldose to an aldonic acid:
Nitric Acid Oxidation: Aldaric Acids
Dilute nitric acid—a stronger oxidizing agent than bromine water—oxidizes both the -CHO
group and the terminal -CH2OH group of an aldose to -CO2H groups, forming dicarboxylic
acids are known as aldaric acids:

In an aldonic acid, one end is oxidised. In an aldaric both end are oxidized
Oxidation to Uronic Acids:
Enzyme-catalyzed oxidation of the primary hydroxyl group at carbon 6 of a hexose yields
auronic acid. if only the -CH2OH end of the aldose is oxidized without affecting the -CHO
group, the product is a monocarboxylic acid called a uronic acid. The reaction can only be
done enzymatically; no chemical reagent is known that can accomplish this selective
oxidation in the laboratory.
Periodate Oxidations: Oxidative Cleavage of Polyhydroxy Compounds
for every C-C bond broken, a C=O bond is formed at each carbon.
Reduction of Monosaccharides: Alditols
Reactions at the Carbonyl Group—
D-fructose exists as an equilibrium between an open-chain form, two pyranose forms (α
andβ), and two furanose forms (α and β). When D-fructose is dissolved in water, the
following equilibrium concentrations are observed: 70% β-pyranose, 2% α-pyranose, 23%
β-furanose, 5% α-furanose, and 0.7% open chain. Despite the fact that the β-pyranose
ring predominates at equilibrium as observed in the laboratory, it is the β-furanose form
of D-fructose that participates in most biochemical pathways.
Disaccharides
The reaction of a monosaccharide with an alcohol yields a glycoside in which the anomeric
-OH group is replaced by an -OR substituent. If the alcohol is itself a sugar, the glycosidic
product is a disaccharide.

Maltose and cellobiose are both reducing sugars because the anomeric carbons on the
right-hand glucopyranose units have hemiacetal groups and are in equilibrium with
aldehyde forms. For a similar reason, both maltose and cellobiose exhibit mutarotation of
α- and β anomers of the glucopyranose unit onthe right.
Unlike most other disaccharides, sucrose is not a reducing sugar and does not undergo
mutarotation. These observations imply that sucrose is not a hemiacetal and suggest
that glucose and fructose must both be glycosides.