160

315

Chapter 25: Carbohydrateshydrates of carbon: general formula Cn(H2O)n

Plants: photosynthesis6 CO2 + H2O C6H12O6 + 6 O2

Polymers: large molecules made up of repeating smaller units (monomer)

Biopolymers: Monomer units:carbohydrates (chapter 25) monosaccharidespeptides and proteins (chapter 26) amino acidsnucleic acids (chapter 28) nucleotides

hν

316

25.1 Classification of Carbohydrates:I. Number of carbohydrate units

monosaccharides: one carbohydrate unit (simple carbohydrates)

disaccharides: two carbohydrate units (complex carbohydrates)

trisaccharides: three carbohydrate unitspolysaccharides: many carbohydrate units

glucose

glucose = lactose

galactose + glucose

polymer = amylose or cellulose

OHOHO

HO

HO

OH

OOHO

HO

HO

OOHO

HO

HO

O

OHOHO

HO

HOOH

OHO

HO

HOO

OOHO

HO

HOO

OHO

HO

HO

OH

O

HO

HO

HO

HOO

CHO

OHH

HHO

OHH

OHH

CH2OH

161

317

II. Position of carbonyl groupat C1, carbonyl is an aldehyde: aldoseat any other carbon, carbonyl is a ketone: ketose

III. Number of carbonsthree carbons: triose six carbons: hexosefour carbons: tetrose seven carbons: heptosefive carbons: pentose etc.

IV. Cyclic form (chapter 25.5)

CHO

OHH

HHO

OHH

OHH

CH2OH

CH2OH

O

HHO

OHH

OHH

CH2OH

glucose(hexose)

(aldohexose)

fructose(hexose)

(ketohexose)

CHO

OHH

OHH

OHH

CH2OH

CHO

HHO

OHH

CH2OH

CHO

OHH

CH2OH

glyceraldehyde(triose)

threose(tetrose)

ribose(pentose)

318

25.2: Depicting carbohydrates stereochemistry: Fischer Projections: 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

(R)-glyceraldehyde

(S)-glyceraldehyde

OHH

CHO

CH2OHCH2OH

C

CHO

HO

H

CHO

CH2OH

H OH

HHO

CHO

CH2OHCH2OH

C

CHO

H

HO

CHO

CH2OH

HO H

162

319

Manipulation of Fischer Projections1. Fischer projections can be rotate by 180° only!

180° 180°

CHO

CH2OH

H OH

CHO

CH2OH

HHO

(R) (R)

CHO

CH2OH

OHH

CHO

CH2OH

HO H

(S) (S)

180 ° 180 °

ValidFischer

projection

ValidFischer

projection

320

a 90° rotation inverts the stereochemistry and is illegal!

90°

90 °

CHO

CH2OH

H OH

(R)

90 °

H

OH

CH2OHOHC

(S)

!

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

163

321

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

holdsteady

120° 120°

holdsteady hold

steady

holdsteady

120°

holdsteady

120°

holdsteady

CHO

CH2OH

H OH

holdsteady

CHO

H

HO CH2OH

CHO

CH2OH

HO H

holdsteady

H

CH2OH

OHC OH

(R) (R)

(S) (S)

322

Assigning R and S Configuration to Fischer Projections1. Assign priorities to the four substitutents according to the Cahn-Ingold-Prelog rules2. Perform the two allowed manipulations of the Fischer projection to place the lowest priority group at the top (or bottom).3. If the priority of the groups 1-2-3 are clockwise then assign the center as R, if 1-2-3 are counterclockwise then assign the center as S.

CH3

H

CO2HH2N

3

2

4

1

1-2-3 clockwise = R

CO2H

CH3

H NH2

2

1

3

4

CO2H

H

H2N CH3

2

3

4

1

CO2H

CH3

H2N H1

2

3

4

place at the top

hold steadyrotate otherthree groupscounterclockwise

H

CH3

HO2C NH212

3

4

1-2-3 counterclockwise = S

164

323

Fischer projections with more than one chiral center:

(2S, 3R)

CHO

HHO

OHH

CH2OH

1

1

2

2 4

43

3

Hold Steady

H

OHOHC

OHH

CH2OH

2

1

4

21

43

3

S

H

OHOHC

OHH

CH2OH

2

1

4

21

43

3

Hold SteadyH

OHOHC

CH2OHHO

H

2

3

4

1

13

4

2

R

S

CHO

HHO

OHH

CH2OH

CHO

HHO

OHH

CH2OH

Threose

3

1

2

4

324

25.3 D, L SugarsGlyceraldhyde- before the R/S convention, stereochemistry was related to

(+)-glyceraldhydeCHO

CH2OH

H OH

CHO

CH2OH

HO H

D-glyceraldehyde L=glyceraldehydeR-(+)-glyceraldhyde(+)-rotation = dextrorotatory = D

D-carbohydrate have the -OH group of the highest numbered chiral carbon pointing to the right in the Fisher projection as in R-(+)-glyceraldhyde

CHO

OHH

HHO

OHH

OHH

CH2OH

D- glucose

CHO

HO H

H OH

HO H

HO H

CH2OH

L- glucose

CHO

OHH

OHH

OHH

CH2OH

D-ribose

CHO

HO H

HO H

HO H

CH2OH

L-ribose

Most carbohydrate in nature are of the D-series

165

325

For carbohydrates, the convention is to put the carbonyl groupat the top for aldoses and closest to the top for ketoses. Thecarbons are numbered from top to bottom.

Carbohydrates are designated as D- or L- according to the stereochemistry of the highest numbered chiral carbon of theFischer projection. If the hydroxyl group is pointing to the rightin the Fischer projection, the sugar is designated as D (Dextro:Latin for on the right side). If the hydroxyl group is pointing tothe left in the Fischer projection, the sugar is designated as L (Levo: Latin for on the left side). Most naturally occurring carbohydrates are of the D-configuration.

H

CHO

OH

HHO

OHH

OHH

CH2OH

D-Glucose

1

CHO

OHH

HHO

HHO

CH2OH

L-Arabinose

1

highest numbered stereogenic carbon

highest numbered stereogenic carbon

2

3

4

56

4

5

3

2

326

24.4 Configuration of the Aldoses:

D- glucose

CHO

OHH

OHH

OHH

CH2OH

D-ribose

CHO

OHH

CH2OH

D-glyceraldehyde

CHO

HHO

OHH

CH2OH

CHO

OHH

OHH

CH2OH

triose tetroses

D-erythrose D-threose

pentoses

CHO

HHO

OHH

OHH

CH2OH

CHO

OHH

HHO

OHH

CH2OH

CHO

HHO

HHO

OHH

CH2OH

D-arabinose D-xylose D-lyxose

CHO

OHH

OHH

OHH

OHH

CH2OH

CHO

HHO

OHH

OHH

OHH

CH2OH

CHO

OHH

HHO

OHH

OHH

CH2OH

CHO

HHO

HHO

OHH

OHH

CH2OH

D-allose D-altrose D-mannose

CHO

OHH

OHH

HHO

OHH

CH2OH

CHO

HHO

OHH

HHO

OHH

CH2OH

CHO

OHH

HHO

HHO

OHH

CH2OH

CHO

HHO

HHO

HHO

OHH

CH2OH

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

hexoses

166

327

25.5 Cyclic structures of Monosaccharides: hemiacetal formation

R1 H

O

+ R2OH

H+

R1 H

OR2HO

hemiacetal

H

O

OH

OH

O

H

cyclic hemiacetal

328

167

329

25.6: Monosaccharide anomers: mutarotationAnomers: the hemiacetal or hemiketal carbon (the carbonyl

carbon of the open form) is a new chiral center and is referred to as the anomeric carbon (hemi-acetal carbonof the closed form)

The hemiacetal forms of pyranoses adopts a chair conformation. The hydroxyl of the new anomeric (acetal)carbon can be axial (α) or equatorial (β). The anomers are diastereomers.

OHO

HO

CH2OH

HOOH

H

OHO

HO

CH2OH

HOH

OH

TransCis

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

CH2OH are trans)

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

CH2OH are cis)

330

The α- and β-anomers are in equilibrium. They 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 anomers

OHO

HO

HO

HOOH

CHO

OHH

HHO

OHH

OHH

CH2OH

OH

HHO

HO

HOO

HO

H

OH

H

HO

HO

HO

O

HO

OHO

HO

HO

HOH

OH

β-anomer

α-anomer

168

331

25.7: Reactions of monosaccharides

OHOHO

HO

HO

OH

CHO

OHH

HHO

OHH

OHH

CH2OH

reacts likea carbonyl

reacts likealcohols

reacts likealcohols

Ester formation:

OHOHO

HO

HOOH

!-D-glucopyranose

H3C O CH3

O O

pyridine

OOO

O

OO

H3C O

CH3

OO CH3

H3C

O

H3C

O

Ether Formation

OHOHO

HO

HOOH

!-D-glucopyranose

OH3COH3CO

H3CO

H3COOCH3

Ag2O, CH3I

332

Glycoside Formation

When R2OH is another carbohydrate unit, complex carbohydrate are formed.

OHOHO

OH

OHHO

OHOHO

OH

OCH3HO

OHOHO

OH

OCH3

HO

+

CH3OH, HCl

methyl !-D-glucopyranoside methyl "-D-glucopyranoside

R1 H

O

+ R2OH

H+

R1 H

OR2HO

hemiacetal

H

O

OH

OH

O

H

cyclic hemiacetal

H+

R2OHR1 H

OR2R2O

acetal

H+

R2OH

glycoside

OR2

O

H

169

333

The Koenigs-Knorr Reaction

OAcOAcO

AcO

AcOOAc

HBr

OAcOAcO

AcO

AcO

Br

ROH, Ag2O

OAcOAcO

AcO

AcOOR

Neighboring group participation directs the stereochemistry of the glycosidation reaction

334

Reduction of Monosaccharides

Oxidation of Monosaccharides: aldoses can be oxidized to aldonic acids with Ag(I) in NH3 (Tollin’s reagent), Cu(II) (Fehling’s or Benedict’s reagent) or Br2.

OHOHO

HO

HO

OH

CHO

OHH

HHO

OHH

OHH

CH2OH

reacts likea carbonyl

NaBH4

CH2OH

OHH

HHO

OHH

OHH

CH2OH

alditol

CHO

OHH

HHO

OHH

OHH

CH2OH

CO2H

OHH

HHO

OHH

OHH

CH2OH

aldonic acid

Ag(I) Ag(0)

NH3

170

335

Reducing sugars: carbohydrates that can be oxidized to aldonicacids.

2-ketose

CHO

OHH

HHO

OHH

OHH

CH2OH

CO2H

OHH

HHO

OHH

OHH

CO2OH

aldaric acid

HNO3, heat

Oxidation to aldaric acids:

336

Killiani-Fischer Synthesis- chain lengthening of monosaccharides

CHO

HHO

OHH

OHH

CH2OH

D-Arabinose

C

HHO

HHO

OHH

OHH

CH2OH

N

C

OHH

HHO

OHH

OHH

CH2OH

N

HCN

HCN

C

HHO

HHO

OHH

OHH

CH2OH

NH

H2, Pd

H

C

OHH

HHO

OHH

OHH

CH2OH

NH

H2, Pd

H

H3O+

H3O+

C

HHO

HHO

OHH

OHH

CH2OH

OH

C

OHH

HHO

OHH

OHH

CH2OH

OH

D-Glucose

D-Mannose

171

337

The Wohl Degradation: chain shortening of monosaccharides

CHO

OHH

HHO

HHO

OHH

CH2OH

H2NOH

C

OHH

HHO

HHO

OHH

CH2OH

HON

oxime

(CH3CO)2O

CH3CO2Na

C

OHH

HHO

HHO

OHH

CH2OH

N

cyanohydrin

CH3ONaCHO

HHO

HHO

OHH

CH2OH

D-galactose D-Lyxose

H

- HCN

- H2O

338

25.8 Stereochemistry of Glucose: The Fischer Proof(. . . as applied to the D-tetroses and D-pentoses)

CHO

OHH

CH2OH

D-(+)-glyceraldehyde

1) KCN2) H2, Pd3) H2O

1) KCN2) H2, Pd3) H2O

Killiani-Fischer synthesis

CHO

HHO

OHH

CH2OH

CHO

OHH

OHH

CH2OH

D-(-)-erythrose

D-(-)-threose

CO2H

OHH

OHH

CO2H

CO2H

HHO

OHH

CO2H

HNO3,

heat

HNO3,

heat

tartaric acid

D-(-)-tartaric acid

172

339

arabonic acid

HNO3,

heat

HNO3,

heat

CO2H

OHH

OHH

OHH

CO2H

CO2H

HHO

OHH

OHH

CO2H

ribonic acid

1) KCN2) H2, Pd3) H2O

1) KCN2) H2, Pd3) H2O

Killiani-Fischer synthesis

D-(-)-ribose

D-(-)-arabinose

CHO

OHH

OHH

CH2OH

D-(-)-erythrose

CHO

OHH

OHH

OHH

CH2OH

CHO

HHO

OHH

OHH

CH2OH

340

1) KCN2) H2, Pd3) H2O

1) KCN2) H2, Pd3) H2O

Killiani-Fischer synthesis

D-(+)-xylose

D-(-)-lyxose

CHO

HHO

OHH

CH2OH

D-(-)-threose

CHO

OHH

HHO

OHH

CH2OH

CHO

HHO

HHO

OHH

CH2OH

lyxonic acid

HNO3,

heat

HNO3,

heat

CO2H

OHH

HHO

OHH

CO2H

CO2H

HHO

HHO

OHH

CO2H

xylonic acid

173

341

CO2H

OHH

OHH

OHH

OHH

CO2H

CO2H

HHO

OHH

OHH

OHH

CO2H

CO2H

OHH

HHO

OHH

OHH

CO2H

CO2H

HHO

HHO

OHH

OHH

CO2H

CO2H

OHH

OHH

HHO

OHH

CO2H

CO2H

HHO

OHH

HHO

OHH

CO2H

CO2H

OHH

HHO

HHO

OHH

CO2H

CO2H

HHO

HHO

HHO

OHH

CO2H

optically active

optically inactive

optically inactive

optically active

optically active

optically active

optically active

optically active

enantiomers

D- glucose

CHO

OHH

OHH

OHH

CH2OH

D-ribose

CHO

HHO

OHH

OHH

CH2OH

CHO

OHH

HHO

OHH

CH2OH

CHO

HHO

HHO

OHH

CH2OH

D-arabinose D-xylose D-lyxose

CHO

OHH

OHH

OHH

OHH

CH2OH

CHO

HHO

OHH

OHH

OHH

CH2OH

CHO

OHH

HHO

OHH

OHH

CH2OH

CHO

HHO

HHO

OHH

OHH

CH2OH

D-allose D-altrose D-mannose

CHO

OHH

OHH

HHO

OHH

CH2OH

CHO

HHO

OHH

HHO

OHH

CH2OH

CHO

OHH

HHO

HHO

OHH

CH2OH

CHO

HHO

HHO

HHO

OHH

CH2OH

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

342

25.9: Disaccharides

When ROH is another carbohydrate unit, a disaccharide formed.

OHO

HO

OH

OHHO

OHO

HO

OH

ORHO

OHO

HO

OH

OR

HO

-or-

ROH

OHOHO

HO

HO

OH

OHOHO

HO

HO

OH

+

glucose glucose

OHOHO

HO

HO

OO

HO

HO

HO

OH

4'

1

maltose(1,4'-!-glycoside)

OHO

HO

HOOH

OHOHO

HO

HOO

cellobiose(1,4'-"-glycoside)

1

4'

174

343

OHO

HO

HOOH

OHOHO

HO

HOO

reducing end

OHHO

HO

HO

O

OHOHO

HO

HOO

H

OHHO

HO

HO

O

OHOHO

HO

HOO

OH

Ag(I)

[O]

+ Ag(0)

cellobiose and maltose are reducing sugar

lactose is a reducing sugar

OHO

HO

HO

OH

O

HO

HO

HO

HOO

reducing end

OHHO

HO

HO

O

O

HO

HO

HO

HOO

HOH

HO

HO

HO

O

O

HO

HO

HO

HOO

OH

Ag(I)

[O] + Ag(0)

1

4'

lactose(1,4'-!-glycoside)

OHOHO

HO

HO

OO

HO

OH

OH

HO

1 !2' "

glucose

fructose

sucrose(1,2'-glycoside) No reducing end

Ag(I)

[O]No reaction

sucrose is nota reducing sugar

344

25.10 Polysaccharides and the their synthesis (please read)Cellulose: glucose polymer made up of 1,4’-β-glycoside linkages

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

O

HO

HO

HO

O

HO

HO

HO

OO

HO

HO

HO

OO

O

HO

HO

HO

OO

HO

HO

HO

OO

HO

HO

HO

OO

H H H H H H

O

OHO

HO

HO

O

O

HO

HO

HO

O

O

HO

HO

HO

O

O

HOHO

O

O

HO

HO

HO

O

O

HO

HO

HO O

HOH HH H H H

175

345

Amylopectin and glycogen: branched amylose related glucose polymers

O

OHO

HO

HO

O

O

HO

HO

HO

O

O

HO

HO

HO

O

O

HOHO

O

O

HO

HO

HO

O

O

HO

HO

HO O

OHO

HO

HO

OO

HO

HO

HO

O

O

H H

H

H

H H H H

25.11 Other Important CarbohydratesDeoxy sugars: carbohydrates that are missing a hydroxyl group

CHO

OHH

OHH

OHH

CH2OH

OHO

HO OHOH

O

OHOH

HO

OH

ribopyranose ribofuranose

CHO

HH

OHH

OHH

CH2OH

OHO

HOOH

O

OH

HO

OH

2-deoxyribopyranose 2-deoxyribofuranose

found in ribonucleic acid (RNA)

found in 2’-deoxyribonucleic acid (DNA)

ribose 2-deoxyribose

346

Eight essential monosaccahrides

CHO

HHO

OHH

OHH

HHO

CH3

L-fucose(6-deoxy-L-galactose

CHO

OHH

HHO

HHO

OHH

CH2OH

D-galactose D- glucose

CHO

OHH

HHO

OHH

OHH

CH2OH

CHO

HHO

HHO

OHH

OHH

CH2OH

D-mannose

CHO

OHH

HHO

OHH

CH2OH

D-xylose

N-acetylglucosamine

CHO

NHCOCH3H

HHO

OHH

OHH

CH2OH

CHO

NHCOCH3H

HHO

HHO

OHH

CH2OH

N-acetylgalactosamine

HH3COCHN

HHO

OHH

OHH

CH2OH

OHH

H H

CO2H

O

N-acetyl-D-neuraminic acid

O

HO

HO

CH3

HO

OH

O

OH

HO

HO

HO

OH

OHOHO

HO

HO

OH

OHOHO

HOOH

OH

OHOHO

HO

OH

OHOHO

HO

HN

OH

O

O

OH

HO

HO

HN

OH

O

OHO

HO2C

O

OHHN

OH

OH

OH

176

347

25.12 Cell-Surface Carbohydrates and Carbohydrate Vaccines (please read): glycobiology

Glycoproteins: glycosides of proteins

OHOHO

HO

HOX Protein

X= -O- or -NH-

HN

NH

O

Ocarbohydrate

serine

HN

NH

O

Ocarbohydrate

threoine

CH3

HN

NH

O

asparagine

O

HN

carbohydrate