Bio Molecules Carbohydrates (1)

8/8/2019 Bio Molecules Carbohydrates (1)

1/32

1

Chapter 25. Biomolecules:Carbohydrates

Based on McMurrys Organic Chemistry , 6th

edition

2

Importance of Carbohydrates

Distributed widely in natureKey intermediates of metabolism (sugars)Structural components of plants (cellulose)Central to materials of industrial products: paper,lumber, fibersKey component of food sources: sugars, flour,vegetable fiberContain OH groups on most carbons in linear chainsor in rings


2/32

2

3

Chemical Formula and NameCarbohydrates have roughly as many Os as Cs(highly oxidized)Since Hs are about connected to each H and O theempirical formulas are roughly (C(H 2O)) n

Appears to be carbon hydrate from formulaCurrent terminology: natural materials that containmany hydroxyls and other oxygen-containing groups

4

Sources

Glucose is produced in plants throughphotosynthesis from CO 2 and H 2OGlucose is converted in plants to other smallsugars and polymers (cellulose, starch)Dietary carbohydrates provide the majorsource of energy required by organisms


3/32

3

5

25.1 Classification of CarbohydratesSimple sugars (monosaccharides) can't be convertedinto smaller sugars by hydrolysis.Carbohydrates are made of two or more simplesugars connected as acetals (aldehyde and alcohol),oligosaccharides and polysaccharidesSucrose (table sugar): disaccharide from twomonosaccharides (glucose linked to fructose),Cellulose is a polysaccharide of several thousand

glucose units connected by acetal linkages (aldehydeand alcohol)A disaccharidederived fromcellulose

6

Aldoses and Ketosesaldo - and keto - prefixes identify the nature of thecarbonyl group-ose suffix designates a carbohydrateNumber of Cs in the monosaccharide indicated byroot (-tri-, tetr-, pent-, hex-)


4/32

4

7

25.2 Depicting Carbohydrate Stereochemistry:Fischer Projections

Carbohydrates have multiple chirality centers andcommon sets of atomsA chirality center C is projected into the plane of thepaper and other groups are horizontal or vertical linesGroups forward from paper are always in horizontalline. The oxidized end of the molecule is alwayshigher on the page (up)The projection can be seen with molecular models

8

Stereochemical Reference

The reference compounds are the two enantiomersof glyceraldehyde, C 3H6O3A compound is D if the hydroxyl group at thechirality center farthest from the oxidized end of thesugar is on the right or L if it is on the left.D-glyceraldehyde is ( R )-2,3-dihydroxypropanalL-glyceraldehyde is ( S )-2,3-dihydroxypropanal


5/32

5

9

The D-Sugar FamilyCorrelation is always with D-(+)-glyceraldehyde(R ) in C-I-P sense

10

Rosanoff Structural Families

The structures show how the D and L familymembers are identified by projection of the bottomchirality centerThe rest of the structure is designated in the name ofthe compound

The convention is still widely used


6/32

6

11

Working With Fischer ProjectionsIf groups are not in corresponding positions, they canbe exchanged three at a time in rotation work withmolecular models to see how this is doneThe entire structure may only be rotated by 180 While R, S designations can be deduced fromFischer projections (with practice), it is best to makemolecular models from the projected structure andwork with the model

12

25.3 D, L Sugars

Glyceraldehyde exists as two enantiomers, firstidentified by their opposite rotation of plane polarizedlightNaturally occurring glyceraldehyde rotates plane-polarized light in a clockwise direction, denoted (+)and is designated (+)-glyceraldehydeThe enantiomer gives the opposite rotation and has a(-) or l (levorotatory) prefixThe direction of rotation of light does not correlate toany structural feature


7/32

7

13

IUPAC Definitions1996Fischer-Rosanoff Convention - according to which (+)-glyceraldehyde, now known to be (R)-2,3-dihydroxypropanal,was named D-glyceraldehyde (with the enantiomer L-glyceraldehyde and its racemate DL-glyceraldehyde) and takento have the absolute configuration represented by the Fischerprojection formula shown below. The atom numbered 1according to normal nomenclature rules is conventionally placedat the top of the main chain, which is drawn vertically and othergroups are drawn on either side of that main chain. Theconvention is still in use for -amino acids and for sugars

D-glyceraldehyde L-glyceraldehyde

IUPAC, Commission on Nomenclature of OrganicChemistry, Section E: Stereochemistry(Recommendations 1974), Pure Appl. Chem . 45 , 11-30(1976)

14

25.4 Configurations of the Aldoses

Stereoisomeric aldoses are distinguished by trivialnames, rather than by systematic designationsEnantiomers have the same names but different D,Lprefixes

R,S designations are difficult to work with when thereare multiple similar chirality centersSystematic methods for drawing and recallingstructures are based on the use of Fischerprojections


8/32

8

15

Four Carbon AldosesAldotetroses have two chirality centersThere are 4 stereoisomeric aldotetroses, two pairsof enantiomers: erythrose and threose D-erythrose is a a diastereomer of D-threose and L-threose

16

Minimal Fischer Projections

In order to work with structures of aldoses moreeasily, only essential elements are shownOH at a chirality center is and the carbonyl is anarrow

The terminal OH in the CH 2OH group is not shown


9/32

9

17

AldopentosesThree chirality centers and 2 3 = 8 stereoisomers, fourpairs of enantiomers: ribose , arabinose , xylose , andlyxose Only D enantiomers will be shown

18

Systematic Drawing

A chirality center is added with each CHOH addingtwice the number of diastereomers and enantiomersEach diastereomer has a distinct name

Start with the fact that they are D Go up to next center in 2 sets of 2

Finish with alternating pairs


10/32

10

19

Apply to AldhexosesThere are eight sets of enantiomers (fromfour chirality centers)

20

25.4 Configurations of theAldohexoses

8 pairs of enantiomers: allose , altrose , glucose ,mannose , gulose , idose, galactose, talose Name the 8 isomers using the mnemonic "All altruistsgladly make gum in gallon tanks"


11/32

11

21

25.5 Cyclic Structures of Monosaccharides:

Hemiacetal Formation

Alcohols add reversibly to aldehydes andketones, forming hemiacetals

22

Internal Hemiacetals of Sugars

Intramolecular nucleophilic addition creates cyclichemiacetals in sugarsFive- and six-membered cyclic hemiacetals areparticularly stableFive-membered rings are furanoses. Six-membered arepyanosesFormation of the the cyclic hemiacetal creates anadditional chirality center giving two diasteromeric forms,desigmated and These diastereomers are called anomersThe designation indicates that the OH at the anomericcenter is on the same side of the Fischer projectionstructure as hydroxyl that designates whether thestructure us D or L


12/32

12

23

Fischer Projection Structures of Anomers:Allopyranose from Allose

24

Converting to Proper Structures

The Fischer projection structures must be redrawn toconsider real bond lengthsNote that all bonds on the same side of the Fischerprojection will be cis in the actual ring structure


13/32

13

25

Pyranose rings have a chair-like geometry with axialand equatorial substituentsRings are usually drawn placing the hemiacetaloxygen atom at the right rear

Conformations of Pyranoses

26

25.6 Monosaccharide Anomers:Mutarotation

The two anomers of D-glucopyranose can becrystallized and purified

-D-glucopyranose melts at 146and its specificrotation, [ ]D = 112.2;

-D-glucopyranose melts at 148155C a specificrotation of [ ]D = 18.7Rotation of solutions of either pure anomer slowlychange due to slow conversion of the pure anomersinto a 37:63 equilibrium mixture ot : calledmutarotation


14/32

14

27

Mechanism of Mutarotation GlucoseOccurs by reversible ring-opening of each anomer tothe open-chain aldehyde, followed by reclosureCatalyzed by both acid and base

28

25.7 Reactions of Monosaccharides

OH groups can be converted into esters andethers, which are often easier to work with than thefree sugars and are soluble in organic solvents.

Esterification by treating with an acid chloride or acidanhydride in the presence of a baseAll OH groups react


15/32

15

29

EthersTreatment with an alkyl halide in the presence ofbasethe Williamson ether synthesisUse silver oxide as a catalyst with base-sensitivecompounds

30

Glycoside Formation

Treatment of a monosaccharide hemiacetal with analcohol and an acid catalyst yields an acetal in whichthe anomeric OH has been replaced by an ORgroup

-D-glucopyranose with methanol and acid gives amixture of and methyl D-glucopyranosides


16/32

16

31

GlycosidesCarbohydrate acetals are named by first citing thealkyl group and then replacing the - ose ending of thesugar with oside Stable in water, requiring acid for hydrolysis

32

Selective Formation of C1-Acetal

Synthesis requires distinguishing the numerous OHgroupsTreatment of glucose pentaacetate with HBr convertsanomeric OH to Br

Addition of alcohol (with Ag 2O) gives a glycoside(KoenigsKnorr reaction)


17/32

17

33

Koenigs-Knorr Reaction Mechanism and anomers of tetraacetyl-D-glucopyranosylbromide give -glycosideSuggests either bromide leaves and cation isstabilized by neighboring acetyl nucleophile from sideIncoming alcohol displaces acetyl oxygen to give glycoside

34

Reduction of Monosaccharides

Treatment of an aldose or ketose with NaBH 4reduces it to a polyalcohol (alditol)Reaction via the open-chain form in thealdehyde/ketone hemiacetal equilibrium


18/32

18

35

Oxidation of MonosaccharidesAldoses are easily oxidized to carboxylic acids by:Tollens' reagent (Ag +, NH3), Fehling's reagent (Cu 2+,sodium tartrate), Benedict`s reagent (Cu 2+ sodiumcitrate)

Oxidations generate metal mirrors; serve as tests forreducing sugars (produce metallic mirrors)

Ketoses are reducing sugars if they can isomerize toaldoses

36

Oxidation of Monosaccharideswith Bromine

Br2 in water is an effective oxidizing reagent forconverting aldoses to carboxylic acid, called aldonicacids (the metal reagents are for analysis only)


19/32

19

37

Formation of Dicarboxylic AcidsWarm dilute HNO 3 oxidizes aldoses to dicarboxylicacids, called aldaric acidsThe CHO group and the terminal CH2OH groupare oxidized to COOH

38

Chain Lengthening: The KilianiFischer Synthesis

Lengthening aldose chain by one CH(OH), analdo pent ose is converted into an aldo hex ose


20/32

20

39

Kiliani-Fischer Synthesis MethodAldoses form cyanohydrins with HCN

Follow by hydrolysis, ester formation, reductionModern improvement: reduce nitrile over a palladiumcatalyst, yielding an imine intermediate that ishydrolyzed to an aldehyde

40

Stereoisomers from Kiliani-FischerSynthesis

Cyanohydrin is formed as a mixture of stereoisomersat the new chirality center, resulting in two aldoses


21/32

21

41

Chain Shortening: The WohlDegradation

Shortens aldose chain by one CH 2OH

42

25.8 Stereochemistry of Glucose: The FischerProof (1891)

Chemical analysis revealed that (+)-glucose has theformula C 6H12O6, and is linear with OH on eachcarbon except carbonyl of aldehydeSuch a structure has four chirality centers and can be

any one of 16 possible stereoisomersSince D and L could not be set, there were 8possibilities to distinguish


22/32

22

43

Possible Structures of D-Glucose

44

Fischers Proof Elongation of ArabinoseArabinose, an aldopentose, is converted byKilianiFischer chain extension into a mixture ofglucose and mannoseGlucose and mannose must differ only at C2


23/32

23

45

Fischers Proof Oxidation withHNO 3

Arabinose isoxidized bywarm HNO 3to an opticallyactive aldaricacidOnly B and Dgive opticallyactive productArabinosemust beeither B or D

46

Fischers Proof: Oxidation of Hexoseswith HNO 3These could allcome fromarabinoseGlucose andmannoseoxidize tooptically activedicarboxylicacidsOnly structures3 and 4 arepossible


24/32

24

47

Fischers Proof: Interchanging EndsReveals the Answer

Oxidation with nitricacid followed byreduction gives twoproducts fromglucose and onlyone from mannoseThis is equivalentto putting aldehydeat C-6

Structure 4 must bemannose since itwould give itselfand 3 must beglucose

48

25.9 Disaccharides

A disaccharide combines a hydroxyl of onemonosaccharide in an acetal linkage with anotherA glycosidic bond between C1 of the first sugar ( or) and the OH at C4 of the second sugar isparticularly common (a 1,4 link)


25/32

25

49

Maltose and CellobioseMaltose: two D-glucopyranose units witha 1,4 --glycoside bond (from starch hydrolysis)Cellobiose: two D-glucopyranose units with a1,4 --glycoside bond (from cellulose hydrolysis)

50

Hemiacetals in Disaccharides

Maltose and cellobiose are both reducing sugarsThe and anomers equilibrate, causingmutarotation


26/32

26

51

You Cant Eat CellobioseThe 1-4- -D-glucopyranosyl linkage in cellobiose isnot attacked by any digestive enzymeThe 1-4- -D-glucopyrnaosyl linkage in maltose is asubstrate for digestive enzymes and cleaves to giveglucose

52

Lactose

A disaccharide that occurs naturally in milkLactose is a reducing sugar. It exhibits mutarotationIt is 1,4- -D-galactopyranosyl- D-glucopyranosideThe structure is cleaved in digestion to glucose andgalactose


27/32

27

53

SucroseTable Sugar is pure sucrose, a disaccharide thathydrolyzes to glucose and fructoseNot a reducing sugar and does not undergomutarotation (not a hemiacetal)Connected as acetal from both anomeric carbons(aldehyde to ketone)

54

25.10 Polysaccharides and TheirSynthesisComplex carbohydrates in which very many simplesugars are linkedCellulose and starch are the two most widelyoccurring polysaccharides


28/32

28

55

CelluloseConsists of thousands of D-glucopyranosyl 1,4 --glucopyranosides as in cellobioseCellulose molecules form a large aggregatestructures held together by hydrogen bondsCellulose is the main component of wood and plantfiber

56

Starch and Glycogen

Starch is a 1,4 --glupyranosyl-glucopyranosidepolymerIt is digested into glucoseThere are two components

amylose , insoluble in water 20% of starch1,4--glycoside polymer

amylopectin , soluble in water 80% of starch


29/32

29

57

AmylopectinMore complex in structure than amyloseHas 1,6 --glycoside branches approximately every25 glucose units in addition to 1,4 --links

58

Glycogen

A polysaccharide that serves the same energystorage function in animals that starch serves inplantsHighly branched and larger than amylopectinup to100,000 glucose units


30/32

30

59

GlycalsTetracetyl glucosyl bromide (see Glycosides) reactswith zinc and acetic acid to form a vinyl ether, aglycal (the one from glucose is glucal )Glycals undergo acid catalyzed addition reactionswith other sugar hydroxyls, forming anhydro disaccharide derivatives

60

Synthesis of Polysaccharides viaGlycalsDifficult to do efficiently, due to many OH groupsGlycal assembly is one approach to being selectiveProtect C6 OH as silyl ether, C3 OH and C4 OHas cyclic carbonate

Glycal C=C is converted to epoxide


31/32

31

61

Glycal CouplingReact glycal epoxide with a second glycal having afree OH (with ZnCl 2 catayst) yields a disaccharideThe disaccharide is a glycal, so it can be epoxidizedand coupled again to yield a trisaccharide, and thenextended

62

25.11 Other Important Carbohydrates

Deoxy sugars have an OH group is replaced by an H.

Derivatives of 2-deoxyribose are the fundamental unitsof DNA (deoxyribonucleic acid)


32/32

63

Amino Sugars OH group is replaced by an NH2

Amino sugars are found in antibiotics such asstreptomycin and gentamicinOccur in cartilage

64

25.12 Cell-Surface Carbohydrates andCarbohydrate Vaccines

Polysaccharides are centrally involved in cellcellrecognition - how one type of cell distinguishes itselffrom anotherSmall polysaccharide chains, covalently bound byglycosidic links to hydroxyl groups on proteins(glycoproteins ), act as biochemical markers on cellsurfaces, determining such things as blood type

Bio Molecules Carbohydrates (1)

Documents

Transcript of Bio Molecules Carbohydrates (1)