Chapitre 22 - Glucides

OH NH2 Me O

HO OH OH O O O O O N H O NH2 OH O N H NHMe CH2i-Pr Cl O H N O Cl

Me O

HO H NH HO2C

H N

H N O

OH OH

Vancomycin (Antibiotique)

202

a) Introduction

Glucides = hydrates de carbone (carbohydrates)

Analyse lmentaire ~ (CH2O)n

OH HO OH OH (+)-glucose OH CHO HO OH OH (-)-fructose OH O OH HO OH (-)-ribose OH OH CHO

C6H12O6 = (CH2O)6
Sucrose C12H22O11 + H2O

C6H12O6 = (CH2O)6
H3O+ Glucose C6H12O6 + Fructose C6H12O6

C5H10O5 = (CH2O)5

Monosaccharide: glucide qu'on ne peut pas cliver par simple hydrolyse (Glucose, Fructose...) Disaccharide: glucide compos de 2 units monosaccharides (Sucrose) Trisaccharide: glucide compos de 3 units monosaccharides (Raffinose) etc. Oligosaccharide: glucide compos de quelques units monosaccharides (3-10) Oligomre, souvent reli des protines = glycoprotine (fibrinogne) Polysaccharide: glucide compos de plusieurs units monosaccharides (>10) Polymre de sucres! Cellulose = Polymre du glucose Matriau de structure des plantes.
203

a) Introduction : Types de monosaccharide

Nature du carbonyle : un aldhyde, un aldose
CHO H H H H OH OH OH OH HO H H H CHO H OH OH OH H HO H H CHO OH H OH OH HO HO H H CHO H H OH OH H H HO H CHO OH OH H OH HO H HO H CHO H OH H OH H HO HO H

6C = hexose
CHO OH H H OH HO HO HO H CHO H H H OH

CH2OH D-(+)-Allose

CH2OH CH2OH D-(+)-Altrose D-(+)-Glucose

CH2OH CH2OH D-(+)-Mannose D-(-)-Gulose

CH2OH D-(+)-Idose

CH2OH D-(+)-Galactose

CH2OH D-(+)-talose

CHO

CHO HO H H H OH OH H HO H

CHO OH H OH HO HO H

CHO H H OH

5C = pentose

H H H

OH OH OH

CH2OH D-(-)-Ribose

CH2OH D-(-)-Arabinose

CH2OH D-(+)-Xylose

CH2OH D-(-)-Lyxose

CHO

CHO HO H H OH CH2OH D-(-)-Throse CHO H OH CH2OH D-(+)-Glycraldhyde

4C = ttrose

H H

OH OH CH2OH

D-(-)-rythrose

3C = triose

204

a) Introduction : Types de monosaccharide

Nature du carbonyle : une ctone, un ctose
CH2OH O H H H OH OH OH HO H H CH2OH O H OH OH H HO H CH2OH O OH H OH H HO H CH2OH O OH H OH

6C = hexose

CH2OH D-psicose

CH2OH D-Fructose

CH2OH D-Sorbose

CH2OH D-Tagatose

CH2OH O

CH2OH O HO H H OH

5C = pentose

H H

OH OH

CH2OH D-Ribulose

CH2OH D-Xylulose

CH2OH CH2OH O CH2OH Dihydroxyacetone H O OH

4C = ttrose
205

CH2OH D-rythrulose

a) Projection de Fisher
(+)-Glycraldhyde HOH2C H CHO CHO H C OH H CHO OH CH2OH H CHO HO CHO CH2OH OH CHO HOH2C H CHO

C OH

R
H R

CH2OH H HO C

HOH2C HO

CHO H HOH2C

CH2OH OH HOH2C C H

OH C R CHO

Double change = mme structure

CHO H HO H H OH H OH OH CH2OH H HO H H

CHO OH H OH OH CH2OH
206

b) Strochimie relative et absolue

Un peu d'histoire...
CHO H OH CH2OH HO H OH (+)-Glycraldhyde D-Glycraldhyde C CHO OHC CHO C OH H OH HO H CH2OH

(-)-Glycraldhyde L-Glycraldhyde

Rosanoff (1906): assigne de faon arbitraire la configuration de la glycraldhyde

Application aux acides amins et autres molcules

CHO HO S H CH2OH

COO H3N H S CH 3 L-(+)-Alanine HO

COOH H

R H

COOH OH

CH2OH

HO H R COOH L-(+)-Acide tartrique

207

L-(-)-Glycraldhyde

L-(+)-Acide lactique

b) Strochimie relative et absolue

La chiralit dans les molcules organiques
LOUIS PASTEUR (1822-1895) : tude de doctorat en chimie l'cole Normale Suprieure. Premiers travaux en cristallisation. tudes en microbiologie et bactriologie (vaccins)

tudes de cristallisation (1848): -Sel d'ammonium et de sodium de l'acide tartrique extrait du vin (nantiomriquement pur). -Sel d'ammonium et de sodium de l'acide tartrique produit chimiquement (racmique). (+)-Acide tartrique O H OH C R ONa H4NO C R H OH O (-)-Acide tartrique OH H4NO S C O H C OH O H ONa

Formation de sels diastroisomres

208

 A. Wohl (1917)

Conversion glycraldhyde en acide tartrique

2 diastroisomres OH C CN

CHO HCN, NH3 C R H H2O OH (+)-Glycraldhyde HO

H HO H C

OH C CN + HO

H H C

OH

OH

1. H2SO4 2. HNO3 O H OH C S OH HO C S H O OH (-)-Acide tartrique OH C R OH O

O H HO H C

Spar par cristallisation

S OH

Acide tartrique mso

Bijvoet (1951)

Dtermine la configuration absolue de l'acide tartrique

OH (+)-Acide tartrique
209

C R OH HO C R H O OH

O H

c) Projection de Haworth : glucose

CHO H HO H H OH H OH OH CH2OH HO HO HO CH2OH CHO OH CH2OH OH HO CHO HO OH

CH2OH O HO C HO + CH2OH O HO C HO OH OH

OH

-D-(+)-Glucopyranose

OH

Norman Haworth (1920-30)

OH OH HO HO O OH OH Pf = 150 C; [] = +19 D

-D-(+)-Glucopyranose CH2OH O OH OH OH -D-(+)-Glucopyranose CH2OH O OH OH OH OH HO HO OH O Pf = 146 C; []D = +112 OH OH

-D-(+)-Glucopyranose

210

c) Projection de Haworth : glucose

Nom (glucose, mannose, etc...) reprsente la strochimie relative des groupements -OH D-sucres: le -OH du bas, est droite; L-Sucres: le -OH du bas, est gauche.
CHO H HO H H OH H OH OH L-(-)-Glucose HO H HO H CHO H OH H OH

CH2OH D-(+)-Glucose

CH2OH D-(+)-Idose

CH2OH O Anomre OH OH H OH HO HO H HO OH OH OH OH

CH2OH O OH OH OH H OH HO HO H HO H
211

Anomre

OH H H -D-(+)-Glucopyranose

OH H OH -D-(+)-Glucopyranose

c) Projection de Haworth : glucose

-D-galactopyranose HO CH OH 2 O HO OH OH HO HO HOH2C HO OH -L-galactopyranose HO HOCH2OH O OH

OH O CH2OH OH OH

OH OH

-D-mannopyranose HOH2C HO HO OH O OH HO

-L-mannopyranose HO OH CH2OH O OH OH O OH HO CH OHOH 2

HOH2C HO HO

O OH

OH

212

c) Projection de Haworth : fructose

OH O OH CH2OH -D-(+)-Fructopyranose (70%) OH HO HO HO CH2 O C CH2OH OH Fructose, forme ouverte HOH2C HO OH O C CH2OH OH HOH2C H CH2OH OH OH O CH2OH

HO

HO

OH OH -D-(+)-Fructopyranose (2%)

HOH2C H

O HO

OH CH2OH

O HO

OH -D-(+)-Fructofuranose (23%)

OH -D-(+)-Fructofuranose (5%)
213

d) Mutarotation

Changement de la valeur d'activit optique avec le temps.

D-glucose a 2 formes cristallines Pf = 146C; []D = +112 Pf = 150C; []D = +19

Solution dans l'eau: []D = +52.7 H OH HO HO H H HO H OH OH H2O H OH HO HO H HO H H OH OH H OH HO HO H H HO OH OH H 64% l'quilibre

36% l'quilibre

214

e) Formation de Glycosides
Mthyl -D-glucopyranoside HOH2C HO HO O OH HCl OH MeOH HOH2C HO HO O OCH3 HOH2C HO HO O OH OCH3

OH Mthyl -D-glucopyranoside

HOH2C HO HO

O OH OH

H Cl

215

HOH2C HO HO

O OH

MeOH

HOH2C HO HO

O OH

MeOH

216

Liens glycosides dans la nature

Sucre HOH2C HO HO O O Aglycone CH2OH AcO COOH Prcurseur de l'acide actylsalicylique (Aspirin)

OH Salicin

retrouv dans l'corce de saule

Hydrolyse des Glycosides
HOH2C HO HO O O OH CH2OH H3O+, H2O HOH2C HO HO CH2OH O OH OH + HO

H OH2 HOH2C HO HO O O OH
217

CH2OH

HOH2C HO HO

O OH

HOH

HOH2C HO HO

O OH

HOH

218

Problmes 22.3-22.5

f) Sucres naturels
HOH2C HO HO glucose O OH OH O O OH CH2OH Fructose
Cl

OH CH2OH O HO galactose OHO HO HO

Cl O HO OH OH O Sucralose O

Raffinose (mlasse) 100x moins sucr que le sucrose O OH O CH2OH

OH Cl

CH2OH Sucrose ou Saccharose

HOH2C HO HO glucose

glucose OHO

OH CH2OH Fructose

O OH O HO CH2OH O OH OH

Maltose (sucre de malte) 3x moins sucr que le sucrose

Cl 2000x plus sucr que le sucrose

OH CH2OH O HO OH galactose

C'est sucr, mais c'est un peptide...

HOH2C O HO

O
O

NH3

H N

O OMe
219

OH glucose OH Lactose (sucre du lait) 5x moins sucr que le sucrose

Aspartame O (Nutrasweet) Ph

200x plus sucr que le sucrose

g) Effet Anomre
HOH2C HO HO HOH2C HO HO O OH OH HCl MeOH + HOH2C HO HO O Mthyl -D-glucopyranoside Majeur OH OCH3

O OH

Mthyl -D-glucopyranoside OCH3 Mineur

Cas des cyclohexanes OCH3 H OCH3 0,60 Kcal/mol Interaction 1,3-diaxiale

Effet strique

220

g) Effet Anomre
Cas des ttrahydropyranes

Effet strolectronique (lectrons et orbitales)

O O O O CH3 CH3

1-2.5 kcal/mol

221

g) Effet Anomre : effet des solvants

O O OMe CCl4 D2O 83% 52% 17% 48% OMe

Polarit (relie au moment dipolaire):

Hydratation
H OH HO HO H H HO H OH OH H2O HO HO H H

H OH HO OH
222

36% l'quilibre

OH H 64% l'quilibre

g) Effet Anomre : effet des solvants

OH

HO

Majeur dans CDCl3 OMe

HO

OMe OH

Majeur dans D2O

223

g) Effet Anomre

HO OH

OH O OH CH2OH HO OH O

OH CH2OH OH

-D-(+)-Fructopyranose (70%)

HO OH

OH O CH2OH HO OH O

CH2OH OH OH

OH -D-(+)-Fructopyranose (2%)

224

h) Ractions des monosaccharides

Formation d'thers
HOH2C HO HO O OH HOH2C HO HO O

MeOH H+

OH D-Glucose

OH OMe Mthyl--D-glucopyranoside NaH, MeI ou MeOSO3Me

MeOH2C MeO MeO

O MeO OH

H3O

MeOH2C MeO MeO

O MeO

OMe

2,3,4,6-Ttra-O-methyl-D-glucopyranoside

Mthyl-2,3,4,6-ttra-O-methyl-D-glucopyranoside

225

h) Ractions des monosaccharides

Conversion en esters
HOH2C HO HO O OH OH Ac2O Pyridine AcOH2C AcO AcO O OAc OAc

Pentaactate de D-glucose

O N + Me O

O Me Me

O N O

O Me Me

O N

OAc

OH

N H

OAc O Me

O O N + N HOAc Me O R R Me

O N O H R OAc
226

HOAc +

h) Ractions des monosaccharides

Synthse de Koenigs-Knorr
HOH2C HO HO AcOH2C AcO AcO

O OH OH

Ac2O Pyridine

O AcO

OAc HBr Acide actique

CH2OH HOH2C HO HO KO O O OH Salicin CH2OH 1. 2. NaOH / H2O AcOH2C AcO AcO O AcO

Br

227

h) Ractions des monosaccharides

AcOH2C AcO AcO O AcO H Br O O

CH2OH K O

228

h) Ractions des monosaccharides

Conversion en actals cycliques : Isopropylidne ou actonide
O HO OH + H+ cat

1,2-diol ou diol vicinal

H SO4H

HO

OH

229

h) Ractions des monosaccharides

Conversion en actals cycliques : Isopropylidne ou actonide
OH CH2OH O HO D-Galactose OH OH O O O O H O

CH2OH O

H+ cat

1,2:3,4-di-O-isopropylidne-D-galactopyranoside

OH CH2OH O HO H HO O OH

OH CH2OH O HO O H O H OH

OH CH2OH O HO O OH
230

h) Ractions des monosaccharides

Conversion en actals cycliques : Isopropylidne ou actonide

HOH2C HO O HO HO D-Mannose

O OH

O O O OO H

2,3:5,6-di-O-isopropylidneD-mannofuranose OH

H+ cat

O O HOH2C HO HO O H cat O
+

O O OH O 1,2:5,6-di-O-isopropylidne-D-glucofuranoside

OH OH D-Glucose

231

O HOH2C HO O HO HO OH D-Mannose HOH2C HO O OO OH HOH2C HO O O OH OH

H+ cat

O O O OO OH H 2,3:5,6-di-O-isopropylidneD-mannofuranose

OH

OH O O OH OH

H+ cat

232

h) Ractions des monosaccharides

Conversion en actals cycliques : Benzylidne
O + OH OH Ph H 1,3-diol H cat O H O Ph Ph
+

H O O

H H

O Ph H

H SO4H Ph

O H

OH

OH

233

Conversion en actals cycliques : Benzylidne

O HOH2C HO HO O OH OMe Mthyl--D-glucopyranoside Ph
+

Ph H O

O HO

O OH OMe

H cat

Mthyl-4,6-O-benzylidne-D-glucopyranoside

Conditions de clivage:

234

h) Ractions des monosaccharides

Raction d'oxydation : glucides rducteurs
Ractif de Tollens CHO H HO H H OH H OH OH CH2OH D-Glucose Ag (NH3)2 OH
+ -

CO2H H HO H H OH H OH OH CH2OH Acide D-gluconique

Ractif de Benedict ou solution de Fehling CHO H HO H H OH H OH OH CH2OH D-Glucose H Cu2+ HO H H CO2H OH H OH OH CH2OH Acide D-gluconique
235

h) Ractions des monosaccharides

Raction d'oxydation

HOH2C HO HO

O OH OH

Br2 H2O

HOH2C HO HO

O OH O

D-Glucose

1,5-D-Gluconolactone

CHO HOH2C HO HO H O OH HO H H OH H OH OH CH2OH HNO3 H HO H H

CO2H OH H OH OH CO2H Acide glucarique

OH D-Glucose

236

h) Ractions des monosaccharides

Clivage oxydatif

NaIO4

O O

O O Na

Priodate de sodium: iode pervalent

O O HO O O O O OH

O O

HO O

O I O

O O

O I OH

O O I O

O O

O O I O

O O

O O

O O

HO
237

h) Ractions des monosaccharides

Clivage oxydatif
O H H C OH H C OH H C OH H Glycrol H H + O OH 2 NaIO4 H + O H

OH H C O H C O H O I O O

H H C O

O H C O H C OH H H2O

I O H C O O H C OH H

OH H C OH H C OH H

238

h) Ractions des monosaccharides

Clivage oxydatif
O CHO H C OH HO C H H C OH H C OH CH2OH D-(+)-Glucose 1 H 5 NaIO4 4 HO 1 C HO H + O C + O C H 1 CH2OH C O HO C H H C OH H C OH CH2OH D-Fructose 1 H 5 NaIO4 3 HO H O C H + 1O C O + O C + O C H H H

Problmes 22.3 22.10

239

h) Ractions des monosaccharides

Rduction

Formation d'alditol
CHO HOH2C HO HO H O OH HO H H OH H OH OH CH2OH NaBH4 H HO H H CH2OH OH H OH OH CH2OH D-Glucitol

OH D-Glucose

CH2OH HO HO O OH OH CH2OH HO H H O H OH OH CH2OH NaBH4 H HO H H

CH2OH OH H OH OH CH2OH D-Glucitol + HO HO H H

CH2OH H H OH OH CH2OH D-Mannitol

240

D-Fructose

Problme 22.11

h) Ractions des monosaccharides

Formation d'osazones partir de la phnylhydrazine
O CH H HO H H OH H OH OH CH2OH Ph-NHNH2 HO H H HC N NHPh N NHPh H OH OH CH2OH Crystallin + PhNH2 + NH3

O CH H OH

241

HC H HO H H

N NHPh OH H OH OH

CH2OH

Problmes 22.12-22.13, 22.22, 22.24-22.28, 22.30, 22.44, travail coopratif 1-2.

242

i) Utilisation des sucres comme source de chiralit en synthse organique

OMe OH HO OH OH D-Mannitol OH 2 quiv. OH TsOH O O OH O O OH NaIO4 NaHCO3 / H2O O (R)-2,3-isopropylideneglycraldhyde O O H

1,2,5,6-di-O-isopropylidneD-mannitol

O O O H

t-BuNH2
H2, Pd/C / MeOH

O O NHt-Bu O N O N S N OH NHt-Bu (-)-Timolol

243

-Bloqueur -adrnergique -Traitement de l'hypertension, l'arythmie, de l'angine et du glaucome