carbohydrate chemistry

CARBOHYDRATE CHEMISTRY

LETS LEARN SOME GREEK!!!!The name glucose comes from the Greek word glykys (γλυκύς), meaning "sweet", plus the suffix "-ose" which denotes a sugar

4 chiral centers give 24 = the 16 stereoisomer s of hexose sugars. Chirality, or "handedness", Greek, (χειρ), kheir: "hand” chiral carbons are enantiomersAlpha α and Beta β are letters in the Greek alphabet

σακχαρωνGreek “sakcharon” = sugar

Carbohydrates • Carbohydrates, or saccharides (saccharo is Greek for ―sugar) are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis.

• Carbohydrates include not only sugar, but also the starches that we find in foods, such as bread, pasta, and rice.

• The term ―carbohydrate comes from the observation that when you heat sugars, you get carbon and water (hence, hydrate of carbon).

Carbohydrates and Biochemistry•Carbohydrates are compounds of tremendous biological importance:–they provide energy through oxidation–they supply carbon for the synthesis of cell components–they serve as a form of stored chemical energy–they form part of the structures of some cells and tissues•Carbohydrates, along with lipids, proteins, nucleic acids, and other compounds are known as biomolecules because they are closely associated with living organisms.

Glucose (a monosaccharide)

Plants:photosynthesis

chlorophyll6 CO2 + 6 H2O C6H12O6 + 6 O2

sunlight (+)-glucose

(+)-glucose starch or cellulose

respiration

C6H12O6 + 6 O2 6 CO2 + 6 H2O + energy

Animalsplant starch (+)-glucose

(+)-glucose glycogen

glycogen (+)-glucose

(+)-glucose fats or aminoacids

respiration

(+)-glucose + 6 O2 6 CO2 + 6 H2O + energy

CLASSIFICATION:

1- Monosaccharides (simple sugars): They can not be hydrolyzed into simpler units. E.g. glucose,

galactose,ribose

2- Oligosaccharides (oligo = few): contain from two to ten monosaccharide units joined in glycosidic bonds. e.g.

• disaccharides (2 units) e.g. maltose and sucrose,• trisaccharides (3 units).....etc.

3-Polysaccharides (poly = many): Also known as glycans. They are composed of more than ten monosaccharide units e.g. starch, glycogen, cellulose.....etc.

Monosaccharides

CLASSIFICATION OF MONOSACCHARIDES

1- According to the number of carbon atoms: .Trioses, contain 3 carbon atoms.• Tetroses, contain 4 carbon atoms.• Pentoses, contain 5 carbon atoms.• Hexoses, contain 6 carbon atoms.• Heptoses, contain 7 carbon atoms.• Octoses. contain 8 carbon atoms.

2- According to the characteristic carbonyl group (aldehyde or ketone group):- Aldo sugars: aldoses:

Contain aldehyde group e.g. glucose, ribose, erythrose and glyceraldehydes.- Keto sugars: ketoses:

Contain ketone group e.g. fructose, ribulose and dihydroxy acetone.

Forms of Monosaccharides:

Trioses:

D- glyceraldehyde Dihydroxyacetone

Tetroses:

D - erythrose

Ketose

CH2OH C = O H -C – OH

CH2 OH

D - erythrulose

Pentoses:

Hexoses:

Heptoses: is a ketose sugar

D - sedoheptulose

It is aptly said that Glyceraldehyde is the ‘Reference Carbohydrate’

Cyanohydrin Formation and Chain Extension.

Kiliani-Fischer Synthesis- a series of reaction that extends carbon chain in a carbohydrate by one carbon and one chiral centre.

HNO3, heat

tartaric acid

D-(-)-tartaric acid

Determination of carbohydrate stereochemistry

D-(+)-glyceraldehyde

1) HCN2) H2, Pd/BaSO43) H2O

Killiani-Fischer synthesis

D-(-)-erythrose

D-(-)-threose

arabonic acid

HNO3, heat

ribonic acid

D-(-)-ribose

D-(-)-arabinose

D-(-)-erythrose

lyxonic acid

HNO3, heat

xylonic acid

D-(+)-xylose

D-(-)-lyxose

D-(-)-threose

optically active

optically inactive

optically active

enantiomers

D- glucose

D-ribose

D-arabinose D-xylose D-lyxose

D-allose D-altrose D-mannose

D-gulose D-idose D-galactose D-talose

Physical Properties of Monosaccharides

• Most monosaccharides have a sweet taste (fructose is sweetest; 73% sweeter than sucrose).

• They are solids at room temperature.• They are extremely soluble in water:• Despite their high molecular weights, the presence of

large numbers of OH groups make the monosaccharides much more water soluble than most molecules of similar MW.

• Glucose can dissolve in minute amounts of water to make a syrup (1 g / 1 ml H2O).

Sugar Relative Sweetness Type• Lactose 0.16 Disaccharide• Galactose 0.22 Monosaccharide• Maltose 0.32 Disaccharide• Xylose 0.40 Monosaccharide• Glucose 0.74 Monosaccharide• Sucrose 1.00 Disaccharide • Invert sugar1.30 Mixture of glucose and

fructose

• Fructose 1.73 Monosaccharide

ISOMERISM

ENANTIOMER OPTICAL EPIMER ISOMER

ANOMER ALDOSE-KETOSE ISOMER

The Stereochemistry of Carbohydrates

• Two Forms of Glyceraldehyde•Glyceraldehyde, the simplest carbohydrate, exists in two isomeric forms that are mirror images of each other:

Stereoisomers • These forms are stereoisomers of each other. • Glyceraldehyde is a chiral molecule — it cannot be superimposed on its mirror image. The two mirror-image forms of glyceraldehyde are enantiomers of each other. • Chirality and Handedness • Chiral molecules have the same relationship to each other that your left and right hands have when reflected in a mirror.

• 11

Chiral Carbons• Chiral objects cannot be superimposed on their mirror images —

e.g., hands, gloves, and shoes.• Achiral objects can be superimposed on the mirror images —

e.g., drinking glasses, spheres, and cubes.• Any carbon atom which is connected to four different groups will

be chiral, and will have two nonsuperimposable mirror images; it is a chiral carbon or a center of chirality.

• –If any of the two groups on the carbon are the same, the carbon atom cannot be chiral.

• Many organic compounds, including carbohydrates, contain more than one chiral carbon.

Van’t Hoff’s 2n ruleWhen a molecule has more than one chiral carbon,each carbon can possibly be arranged in either theright-hand or left-hand form, thus if there are n

chiral carbons, there are 2n possible stereoisomers.

Maximum number of possible stereoisomers = 2n

Can you tell no. of possible stereoisomers of CHOLESTEROL?

D and L isomers (Enantiomers) Enantiomers :

They are the mirror image of each others.

CHO CHO H - C– OH HO-C-H CH2OH CH2OH D-Glyceraldehyde L-Glyceraldehyde

Carbohydrates are designated as D- or L- according to the stereochemistry of the highest numbered chiral carbon of theFischer 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.

L- glucose

D-Glucose

L-Arabinose

highest numbered "chiral" carbon

D-Arabinose

What’s So Great About Chiral Molecules?

•Molecules which are enantiomers of each other have exactly the same physical

properties (melting point, boiling point, index of refraction, etc.) but not their

interaction with polarized light.••Polarized light vibrates only in one plane;

it results from passing lights through polarizing filter

Optical Activity•A levorotatory(–) substance rotates polarized light to the left

[e.g., l-glucose; (-)-glucose] .

••A dextrorotatory(+) substance rotates polarized light to the right [e.g., d-glucose; (+)-glucose] .

••Molecules which rotate the plane of polarized light are

optically active .••Many biologically important molecules are chiral and

optically active. Often, living systems contain only one of the possible stereochemical forms of a compound, or they are

found in separate system .•–D-lactic acid is found in living muscles; D-lactic acid is present in sour milk.•–In some cases, one form of a molecule is beneficial, and the enantiomer is a poison (e.g.,

thalidomide).•–Humans can metabolize D-monosaccharides but not L-isomers; only L-amino acids are used

in protein synthesis

The Aldotetroses. Glyceraldehyde is the simplestcarbohydrate (C3, aldotriose, 2,3-dihydroxypropanal). The nextcarbohydrate are aldotetroses (C4, 2,3,4-trihydroxybutanal).

D-glyceraldehyde

aldotriose

L-glyceraldehyde

aldotetroses

D-erythrose

D-threose

L-erythrose

L-threose

Aldopentoses and Aldohexoses.Aldopentoses: C5, three chiral carbons, eight stereoisomers

Aldohexoses: C6, four chiral carbons, sixteen stereoisomers

D-ribose

D-arabinose D-xylose D-lyxose

D- glucose

D-allose D-altrose D-mannose

D-gulose D-idose D-galactose D-talose

Fischer Projections and the D-L Notation. Representation of a three-dimensional molecule as a flat structure. Tetrahedral carbon represented by two crossed lines:

vertical line is going backbehind the plane of the paper (away from you)

horizontal line is coming out of the plane of the page (toward you)

carbonsubstituent

(+)-glyceraldehyde

(-)-glyceraldehyde

OHHCHO

CH2OHCH2OHC

CH2OHH OH

HHOCHO

CH2OHCH2OHC

CH2OHHO H

Manipulation of Fischer Projections1. Fischer projections can be rotate by 180° (in the plane of the

page) only!

180° 180°

CH2OHH OH

CH2OHHHO

(R) (R)

CH2OHOHH

CH2OHHO H

(S) (S)

180 ° 180 °

ValidFischer

projection

ValidFischer

projection

a 90° rotation inverts the stereochemistry and is illegal!

CH2OHH OH

OHCH2OHOHC

This is not the correct conventionfor Fischer projections

Should be projecting toward youShould be projecting away you

This is the correct conventionfor Fischer projections and isthe enantiomer

2. If one group of a Fischer projection is held steady, the other three groups can be rotated clockwise or counterclockwise.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.QuickTime™ and a

TIFF (Uncompressed) decompressorare needed to see this picture. QuickTime™ and a

TIFF (Uncompressed) decompressorare needed to see this picture.

holdsteady

120° 120°

holdsteady hold

steady

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.QuickTime™ and a

holdsteady

120°QuickTime™ and a

holdsteady

CH2OHH OH

holdsteady

HO CH2OH

holdsteady

OHC OH

(R) (R)

(S) (S)

Cyclic Forms of Carbohydrates: Furanose Forms.

O+ R2OH

hemiacetal

H+, R2OH

OR2R2O

acetal

(Ch. 17.8)

cyclic hemiacetal

H+, ROH

mixed acetal (glycoside)

Ch. 25.13

In the case of carbohydrates, cyclization to the hemiacetal creates a new chiral center.

Converting Fischer Projections to Haworth formulas

CH2OHH

D-erythrose

Cyclic Forms of Carbohydrates: Pyranose Forms.

glucopyranose

ribopyranose

D-ribose

new chiral center

HHOH2C

D-glucose

new chiral center

Two types of pyranose form

Chair form Boat form

CHAIR form is thermodynamically more stable

Substituents on the ring carbons may be either axial (ax), projecting parallel to the vertical axis through the ring, or equatorial (eq), projecting roughly perpendicular to this axis.Two conformers such are these are not readily Interconvertible without breaking the ring. However, when the molecule is “stretched” (by atomic force microscopy), an input of about 46 kJ of energy per mole of sugar can force the interconversion of chair forms. Generally, substituents in the equatorial positions are less sterically hindered by neighboring substituents, and conformers with bulky substituents in equatorial positions are favored. • Another conformation, the “boat” is seen only in

derivatives with very bulky substituents.

Mutarotation and the Anomeric Effect. The hemiacetalor 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.

-D-Glucopyranose (36%)(-anomer: C1-OH and

CH2OH are trans)

-D-Glucopyranose (64%)(-anomer: C1-OH and

CH2OH are cis)OHO

HOOHCHO

OHHHHOOHHOHH

D-glucose

α, D-glucose D-glucose , D-glucose (+110 ) (+52.5) (+17.2 )

Epimers:• Two monosaccharides differ only in the

configuration around one specific carbon atom.

• The D-glucose and D-mannose are epimers with respect to carbon atom 2,

• D-glucose and D-galactose are epimers with respect to carbon atom 4.

Aldose-Ketose isomerism:

Two monosaccharides have the same molecular formulae but differ in their functionl groups.

• one has an aldehyde group (aldose e.g. glucose)

• the other has a ketone group (Ketose e.g. fructose).

Monosaccharides of physiologic importance

1-Pentoses: *-D-ribose is a structural element of ribonucleic

acid (RNA)and coenzymes e.g. ATP, NAD, NADP and others. D-ribose-phosphate and D-ribulose-5-phosphate are formed from glucose in the body (HMS).

*2-deoxy D-ribose enters in the structure of DNA.*D-lyxose: constituent of lyxoflavin in human

myocardium.Lot of experiments are going to establish it as a potent myocardial infarction marker.

2-Hexoses:1- D-glucose (grape sugar, Dextrose as D-

glucose is dextrorotatory ). • It is the sugar carried by the blood

(normal plasma level 70-100 mg/dL) and the principal one used by the tissues.

• It is found in fruit juices • obtained by hydrolysis of starch, cane

sugar, maltose and lactose.

2- D-Fructose (honey sugar = levulose as D-fructose is levorotatory).

• It is found in fruit juices (fruit sugar ) • Obtained from sucrose by hydrolysis. • It is present in the semen in pyranose form3- D-galactose:• It is a constituent of galactolipids and

glycoprotein in cell membranes and extracellular matrix.

Important properties of monosaccharides

Iodocompounds

Glucose when heated with conc. Hydroiodic acid loses all its oxygen and converted to Iodohexane.

This suggests that glucose has no branched chain.

Glucose conc.HI Iodohexane

Ester Formation

The – OH groups of monosaccharides can form esters with acids (phosphate & sulfate).

Phosphate esters: Glucose – 1 – phosphate Glucose – 6 – phosphate

Sulfate esters: Galactose – 3 – sulfate

Glucose – 6 - Phosphate

Sugar as reducing agent The monosaccharides and most of the

disaccharides are rather strong reducing agents, particularly at high pH.

At alkaline pH aldehyde or keto group tautomerizes to form highly reactive ENEDIOL group. This group has strong reducing property.

H C OH

C OH 1,2 enediol form

Trommer’s test-precursor of BENEDICT’S testCuSO4 + 2NaOH Cu(OH)2 + Na2SO4 (bluish white)

2Cu(OH)2 2 CuOH + H2O + O

Cu2O + H2O (red)Trommer’s test is not convenient enough and later Benedict’s test replaced it.

Copper(I) oxide(red-orange ppt)

Benedict’s reagent contains CuSO4,sodium carbonate and sodium citrate.Ammoniac silver nitrate solution may be reduced to metallic silver, producing a mirror-TOLLEN’s TestAlkaline Bismuth solution, known as Nylander’s solution, deposits black metallic bismuth on reduction.Picric acid in alkaline medium is reduced to picramic acid. Color changes from yellowish orange to mahogany red.In acid solution sugar reduces less vigorously.Barfoed’s test utilizes this fact for distinguishing monosaccharides from reducing disaccharides.

Benedict’s Reagent(blue)

Reaction with strong alkalis

The sugar caramelises and produces a series of decomposition products,yellow and brown pigments develop,salts may form, many double bonds are formed between C-atoms.

Action of strong acid on monosaccharides With conc. Mineral acids the

monosaccharides get decomposed. Pentoses yield cyclic aldehyde

‘furfural’. Hexoses are decomposed to

‘hydroxymethyl furfural’ which decomposes further to produce laevulinic acid,CO,CO2

The furfural products can condense with certain organic phenols to form compounds having characteristic color. It forms the basis of certain tests used for detection of sugars.Molisch’s Test: With alpha-naphthol (in alcoholic solution)gives purple ring. A sensitive reaction but not specific. It is used as Group test of carbohydrate.Seliwanoff’s test:With resorcinol, a cherry red colour is produced. It is characteristic of D-fructose. Other tests are anthrone test, Bial-orcinol test

OSAZONE formation Emil Fischer done this job to detect

various sugars. Used to differentiate simple sugar by their

varied form of osazone and rate of osazone formation.

PREPARATION: they are obtained by adding a mixture of phenylhydrazine hydrochloride and sodium acetate to the sugar solution and heating in boiling water bath for 30 to 45 mins.The solution is allowed to cool slowly by itself.crystals are formed .A coverslip preparation is made on a clean slide and seen under microscope.

Mullikin’s figures sugar Glucose Fructose Sucrose Maltose

Lactose

Time(minutes)4-5230-45 after hydrolysisOsazone soluble in hot water Osazone soluble in hot water

Principle Free carbonyl group of sugars react

eith phenylhydrazine to form phenylhydrazone

With excess phenylhydrazine, the adjacent C-atom of carbonyl group react with phenylhydrazine to form yellow compounds called osazone.

Oxidation of sugar1. Aldonic acid: oxidation of an aldoses with Br2-water converts the aldehyde group to a carboxyllic group D-Glucose D-gluconic acid2.Saccharic acid or aldaric acid: oxidation of aldoses with conc.HNO3 under proper conditions convert both aldehyde and primary alcohol group to –COOH group,forming dibasic sugar acids, the Saccharic acid or aldaric acid.D-Glucose D-Glucaric acid

D-Galactose D-Mucic acid 76

3. Uronic acid: When only the primary alcohol group of an aldose is oxidized to –COOH group, without oxidation of aldehyde group, a uronic acid is formed.D-Glucose D-Glucuronic acidD-galactose D-Galacturonic acidDue to presence of free –CHO group they exert reducing action.Biomedical importance

Reduction Carbonyl groups can be reduced to alcohols

(catalytic hydrogenation)

Sweet but slowly absorbed Glucose is reduced to sorbitol (glucitol) Xylose can be reduced to xylitol Once reduced – less reactive; not absorbed

H O[H]

Glceraldehyde & dihydroxyacetone to Glycerol.

Ribose to Ribitol. Glucose to Sorbitol. Galactose to Dulcitol. Mannose to Mannitol. Fructose to Sorbitol & Mannitol

Glycerol Present in the structure of many lipids.

Ribitol Enters in the structure of Riboflavin.

Myo-inositol One of the isomers of inositol. A hydroxylated cyclohexane. Present in the structure of a

phospholipid termed phosphatidyl inositol.

Interconversion of sugars Glucose, Fructose and Mannose

differ from each other only arrond C1- C3.So they are interconvertible in weak alkaline solution such as Ba(OH)2 or Ca(OH)2.

This is due to same ENEDIOL formation during tautomerization.This is called Lobry de Bruyn-Van Ekenstein Reaction

HO ,H2O

D-glucose D-mannose

(R) (S)

D-fructose

HO ,H2O

Other sugar derivatives of biomedical importance L-ascorbic acid Phytic acid Deoxy sugar Amino sugar Amino sugar acids Glycosides

L – Ascorbic acid

O = C Due to lack of

HO – C enzymes it bec-

HO – C O omes a VITAMIN

H – C for human beings

HO – C - H CH2OH Glucuronic acid is reduced to L-Gulonic acid and

then converted through L-Gulonolactone to L-Ascorbic acid in plants and most higher animals.

Phytic acid

The hexaphosphoric ester of inositol.

Forms insoluble salts with Ca2+, Mg2+, Fe2+ & Cu2+

Prevent their absorption from diet in the small intestine.

So it is better to avoid maize and legumes in diet of anaemic patient with iron rich diet or haematinic drugs.

Deoxysugars

Deoxyribofuranose Present in DNA.

L-Fucose 6-deoxy-L-galactose Important component of some cell

membrane glycoproteins & blood group antigens.

Aminosugars

Formed from the corresponding monosaccharide by replacing the –OH group at C2 with an amino (NH2) group.

Are important constituents of GAGs & some types of glycolipids eg gangliosides.

Are conjugated with acetic acid &/or sulfate to form different derivatives.

Aminosugars

Glucosamine Galactosamine Mannosamine Glucosamine – 2,6 – bisulfate

(heparin) N-acetyl-glucosamine (hyaluronic

acid) N-acetyl-galactosamine

(chondroitin sulfate)

Amino sugar

Glycosylamine• Anomeric –OH group is

replaced by –NH2• e.g glucosylamine

Glycosamine• -OH group attached to

carbon atom other than the anomeric one.

• e.g glucosamine

Glucosamine

Aminosugars Acids

• Are formed of 6-C aminosugars linked to 3-C acid.

• Examples:– Neuraminic acid: (Mannosamine + Pyruvic

acid)– N-acetylneuraminic acid (Sialic acid)– Muramic acid (glucosamine + lactic acid)

Sialic Acid (NANA)

Enters in the structure of may glycolipids & glycoproteins.

Forms an important structure of cell membrane & has many important functions: It is important for cell recognition & interaction. It is an important constituent of cell membrane

receptors. It plays an important role in cell membrane

transport systems.

Neuraminic Acid

Glycosides

Formed by a reaction between the anomeric carbon (in the form of hemiacetal or hemiketal) with alcohols or phenols.

Are named according to the reacting sugar.

Any glycosidic linkage is named according to the type of parent sugar eg glucosidic, galactosidic or fructosidic linkages.

Types of Glycosides

Monosaccharide units may condense in the form of di-, oligo- & polysaccharides where the second sugar reacts as an alcohol & condenses with the anomeric carbon by removal of H2O.

A sugar may also condense with a non-sugar radical (aglycon) Nucleoside: (pentose sugar +

nitrogenous base)

Biomedically important Glycosides

• Cardiac glycosides: obtained from digitalis

• They all contain steroids as aglycone.• Digitalis glycosides include digitoxin,

gitoxin, gitalin and digoxin• Digoxin is class V antiarrhythmic drug

according to Vaughan Williams classification.

• Used in supraventricular arrhythmia especially

heart failure with atrial fibrillation

• Contraindicated in ventricular tachycardia.• Chemically, Digitonin 4Galactose +Xylose+digitogenin (aglycone)

OUABAIN: It gains interest as class 1C

antiarrhythmic drug that inhibit active transport of sodium in myocardium in vivo.It prevents paroxysmal atrial fibrillation.

PHLORIDZIN: Obtained from the root and bark of apple tree. It blocks transport of sugar across mucosal cells

of small intestine and renal tubular epithelium.Displaces Na+ from the binding site of carrier

protein and prevents the binding of sugar molecule and produces glycosuria.

STREPTOMYCIN , the well known antibiotic is also a Glycoside.

carbohydrate chemistry

Education

milk carbohydrate: lactose - courseware

investigating carbohydrate isomers by ims-cid-ims...

chuong ii carbohydrate - cdtp4.files. · pdf file1 chƯƠng...

fulltext01_2 efficient carbohydrate synthesis by controlled ...

carbohydrate slide

คาร์โบไฮเครตเมแทบอลิซึม...

carbohydrate digestion & metabolism

carbohydrate polymer

predigested carbohydrate (n2n)

carbohydrate metabolism - biochemistry notes · pdf...

sintesis obat - 03 carbohydrate

sci 241 carbohydrate presentation

new methods in carbohydrate chemistry: dehydrative

advances in carbohydrate chemistry and...

computational characterisation of mesogenes containing...

carbohydrate 1

nah019 carbohydrate chemistry - -...

chapter 2. functional carbohydrate -...

carbohydrate metabolism

carbohydrate chemistry:-